@article{MTMT:34798551,
	title = {Structural basis for autoinhibition by the dephosphorylated regulatory domain of Ycf1},
	url = {https://m2.mtmt.hu/api/publication/34798551},
	author = {Khandelwal, N.K. and Tomasiak, T.M.},
	doi = {10.1038/s41467-024-46722-w},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {15},
	unique-id = {34798551},
	issn = {2041-1723},
	abstract = {Yeast Cadmium Factor 1 (Ycf1) sequesters glutathione and glutathione-heavy metal conjugates into yeast vacuoles as a cellular detoxification mechanism. Ycf1 belongs to the C subfamily of ATP Binding Cassette (ABC) transporters characterized by long flexible linkers, notably the regulatory domain (R-domain). R-domain phosphorylation is necessary for activity, whereas dephosphorylation induces autoinhibition through an undefined mechanism. Because of its transient and dynamic nature, no structure of the dephosphorylated Ycf1 exists, limiting understanding of this R-domain regulation. Here, we capture the dephosphorylated Ycf1 using cryo-EM and show that the unphosphorylated R-domain indeed forms an ordered structure with an unexpected hairpin topology bound within the Ycf1 substrate cavity. This architecture and binding mode resemble that of a viral peptide inhibitor of an ABC transporter and the secreted bacterial WXG peptide toxins. We further reveal the subset of phosphorylation sites within the hairpin turn that drive the reorganization of the R-domain conformation, suggesting a mechanism for Ycf1 activation by phosphorylation-dependent release of R-domain mediated autoinhibition. © The Author(s) 2024.},
	keywords = {DEPHOSPHORYLATION; PEPTIDES; INHIBITOR; metabolism; PEPTIDE; PEPTIDE; GENETICS; ARTICLE; YEAST; ATP-Binding Cassette Transporters; Saccharomyces cerevisiae; Saccharomyces cerevisiae; GLUTATHIONE; GLUTATHIONE; nonhuman; TOPOLOGY; cadmium; cadmium; cadmium; Cryoelectron Microscopy; unclassified drug; Adenosine Triphosphate; protein structure; ABC transporter; cell vacuole; TOXIN; chemical parameters; detoxification; detoxification; Saccharomyces cerevisiae Proteins; Autoinhibition; Saccharomyces cerevisiae protein; wxg peptide; yeast cadmium factor 1},
	year = {2024},
	eissn = {2041-1723}
}

@article{MTMT:34798555,
	title = {Functional Consequences of CFTR Interactions in Cystic Fibrosis},
	url = {https://m2.mtmt.hu/api/publication/34798555},
	author = {Ramananda, Y. and Naren, A.P. and Arora, K.},
	doi = {10.3390/ijms25063384},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34798555},
	issn = {1661-6596},
	abstract = {Cystic fibrosis (CF) is a fatal autosomal recessive disorder caused by the loss of function mutations within a single gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CFTR is a chloride channel that regulates ion and fluid transport across various epithelia. The discovery of CFTR as the CF gene and its cloning in 1989, coupled with extensive research that went into the understanding of the underlying biological mechanisms of CF, have led to the development of revolutionary therapies in CF that we see today. The highly effective modulator therapies have increased the survival rates of CF patients and shifted the epidemiological landscape and disease prognosis. However, the differential effect of modulators among CF patients and the presence of non-responders and ineligible patients underscore the need to develop specialized and customized therapies for a significant number of patients. Recent advances in the understanding of the CFTR structure, its expression, and defined cellular compositions will aid in developing more precise therapies. As the lifespan of CF patients continues to increase, it is becoming critical to clinically address the extra-pulmonary manifestations of CF disease to improve the quality of life of the patients. In-depth analysis of the molecular signature of different CF organs at the transcriptional and post-transcriptional levels is rapidly advancing and will help address the etiological causes and variability of CF among patients and develop precision medicine in CF. In this review, we will provide an overview of CF disease, leading to the discovery and characterization of CFTR and the development of CFTR modulators. The later sections of the review will delve into the key findings derived from single-molecule and single-cell-level analyses of CFTR, followed by an exploration of disease-relevant protein complexes of CFTR that may ultimately define the etiological course of CF disease. © 2024 by the authors.},
	keywords = {Humans; MUTATION; MUTATION; metabolism; signal transduction; signal transduction; human; Quality of Life; Quality of Life; personalized medicine; cystic fibrosis; cystic fibrosis; cystic fibrosis; CFTR protein, human; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator; Precision Medicine; CFTR modulators; CFTR interactors; single-cell analyses of CFTR},
	year = {2024},
	eissn = {1422-0067}
}

@{MTMT:34798244,
	title = {CFTR Modulators: From Mechanism to Targeted Therapeutics},
	url = {https://m2.mtmt.hu/api/publication/34798244},
	author = {Yeh, H.-I. and Sutcliffe, K.J. and Sheppard, D.N. and Hwang, T.-C.},
	booktitle = {Handbook of Experimental Pharmacology},
	doi = {10.1007/164_2022_597},
	volume = {283},
	unique-id = {34798244},
	abstract = {People with cystic fibrosis (CF) suffer from a multi-organ disorder caused by loss-of-function variants in the gene encoding the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Tremendous progress has been made in both basic and clinical sciences over the past three decades since the identification of the CFTR gene. Over 90% of people with CF now have access to therapies targeting dysfunctional CFTR. This success was made possible by numerous studies in the field that incrementally paved the way for the development of small molecules known as CFTR modulators. The advent of CFTR modulators transformed this life-threatening illness into a treatable disease by directly binding to the CFTR protein and correcting defects induced by pathogenic variants. In this chapter, we trace the trajectory of structural and functional studies that brought CF therapies from bench to bedside, with an emphasis on mechanistic understanding of CFTR modulators. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.},
	keywords = {Humans; MUTATION; MUTATION; metabolism; GENETICS; PHARMACOLOGY; CHLORIDE CHANNELS; signal transduction; signal transduction; human; nonhuman; biosynthesis; protein targeting; Biophysics; BIOCHEMISTRY; protein structure; cystic fibrosis; cystic fibrosis; cystic fibrosis; cystic fibrosis; ABC TRANSPORTERS; CFTR protein, human; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator},
	year = {2024},
	pages = {219-247}
}

@article{MTMT:33949969,
	title = {CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway},
	url = {https://m2.mtmt.hu/api/publication/33949969},
	author = {Choi, Kyung-Mi and Cho, Sung-Hee and Kim, Jung Hak and Kim, Ae-Rhee Lilian and Kong, Xiangmudong and Yoon, John C.},
	doi = {10.1016/j.jcf.2022.08.012},
	journal-iso = {J CYST FIBROS},
	journal = {JOURNAL OF CYSTIC FIBROSIS},
	volume = {22},
	unique-id = {33949969},
	issn = {1569-1993},
	abstract = {Background: Cystic fibrosis (CF) is characterized by reduced growth and lower body weight, which are multifactorial. CF mouse models lack key disease characteristics that predispose to a negative energy bal-ance, such as pulmonary infections or exocrine pancreatic insufficiency, and yet they still exhibit a growth defect and an abnormally increased energy expenditure. Whether adipocyte thermogenesis contributes to the elevated resting energy expenditure in CF mice is unknown. Methods: We examined the expression of CFTR in thermogenic brown adipose tissue (BAT) and investi-gated a functional role for CFTR using BAT-specific CFTR null mice (CFTRBATKO). Results: The CFTR protein is expressed in mouse BAT at levels comparable to those in the lungs. BAT-specific inactivation of CFTR in mice increases whole-body energy expenditure associated with sympa-thetic stimulation by cold exposure. Weight gain on a high-fat diet is attenuated in these mice. How-ever, CFTR-deficient brown adipocytes themselves have impaired, rather than enhanced, thermogenic re-sponses. These cells feature decreased lipolysis and blunted activation of the cAMP/PKA signaling pathway in response to adrenergic stimulation. This suggests that compensatory heat production in other tissues likely accounts for the increased systemic energy expenditure seen in CFTRBATKO mice. Conclusions: Our data reveal a new role for CFTR in the regulation of adipocyte thermogenesis. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )},
	keywords = {THERMOGENESIS; CFTR; brown adipocyte; cAMP-PKA pathway},
	year = {2023},
	eissn = {1873-5010},
	pages = {132-139},
	orcid-numbers = {Choi, Kyung-Mi/0000-0001-5517-1796}
}

@article{MTMT:33755807,
	title = {Blue flash sheds light on the roles of individual phosphoserines in CFTR channel activation},
	url = {https://m2.mtmt.hu/api/publication/33755807},
	author = {Csanády, László},
	doi = {10.1085/jgp.202313336},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {155},
	unique-id = {33755807},
	issn = {0022-1295},
	year = {2023},
	eissn = {1540-7748},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:34120853,
	title = {Cell signaling and regulation of CFTR expression in cystic fibrosis cells in the era of high efficiency modulator therapy},
	url = {https://m2.mtmt.hu/api/publication/34120853},
	author = {Ghigo, A. and De, Santi C. and Hart, M. and Mitash, N. and Swiatecka-Urban, A.},
	doi = {10.1016/j.jcf.2022.12.015},
	journal-iso = {J CYST FIBROS},
	journal = {JOURNAL OF CYSTIC FIBROSIS},
	volume = {22},
	unique-id = {34120853},
	issn = {1569-1993},
	abstract = {Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP- and protein kinase A (PKA)-regulated channel, expressed on the luminal surface of secretory and absorptive epithelial cells. CFTR has a complex, cell-specific regulatory network playing a major role in cAMP- and Ca2+-activated secretion of electrolytes. It secretes intracellular Cl– and bicarbonate and regulates absorption of electrolytes by differentially controlling the activity of the epithelial Na+ channel (ENaC) in colon, airways, and sweat ducts. The CFTR gene expression is regulated by cell-specific, time-dependent mechanisms reviewed elsewhere [1]. This review will focus on the transcriptional, post-transcriptional, and translational regulation of CFTR by cAMP-PKA, non-coding (nc)RNAs, and TGF-β signaling pathways in cystic fibrosis (CF) cells. © 2022 European Cystic Fibrosis Society},
	keywords = {Humans; COLON; metabolism; GENETICS; ARTICLE; signal transduction; signal transduction; signal transduction; human; epithelium cell; Calcium ion; enzyme activity; Gene Expression; human cell; protein expression; ELECTROLYTE; BICARBONATE; Electrolytes; cyclic AMP dependent protein kinase; cyclic AMP; cystic fibrosis; cystic fibrosis; endogenous compound; genetic transcription; CFTR protein, human; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator; epithelial sodium channel; airway; TGF beta signaling; untranslated RNA; Sweat; Epithelial Sodium Channels},
	year = {2023},
	eissn = {1873-5010},
	pages = {S12-S16}
}

@article{MTMT:34197790,
	title = {Structure basis of CFTR folding, function and pharmacology},
	url = {https://m2.mtmt.hu/api/publication/34197790},
	author = {Hwang, T.-C. and Braakman, I. and van, der Sluijs P. and Callebaut, I.},
	doi = {10.1016/j.jcf.2022.09.010},
	journal-iso = {J CYST FIBROS},
	journal = {JOURNAL OF CYSTIC FIBROSIS},
	volume = {22},
	unique-id = {34197790},
	issn = {1569-1993},
	abstract = {The root cause of cystic fibrosis (CF), the most common life-shortening genetic disease in the Caucasian population, is the loss of function of the CFTR protein, which serves as a phosphorylation-activated, ATP-gated anion channel in numerous epithelia-lining tissues. In the past decade, high-throughput drug screening has made a significant stride in developing highly effective CFTR modulators for the treatment of CF. Meanwhile, structural-biology studies have succeeded in solving the high-resolution three-dimensional (3D) structure of CFTR in different conformations. Here, we provide a brief overview of some striking features of CFTR folding, function and pharmacology, in light of its specific structural features within the ABC-transporter superfamily. A particular focus is given to CFTR's first nucleotide-binding domain (NBD1), because folding of NBD1 constitutes a bottleneck in the CFTR protein biogenesis pathway, and ATP binding to this domain plays a unique role in the functional stability of CFTR. Unraveling the molecular basis of CFTR folding, function, and pharmacology would inspire the development of next-generation mutation-specific CFTR modulators. © 2022},
	keywords = {Humans; MUTATION; MUTATION; GENETICS; ARTICLE; signal transduction; signal transduction; human; protein phosphorylation; Protein Folding; Protein Folding; Protein Folding; PROTEIN FUNCTION; Adenosine Triphosphate; Adenosine Triphosphate; protein domain; MODULATOR; protein structure; BIOGENESIS; ABC transporter; CFTR; cystic fibrosis; cystic fibrosis; CFTR protein, human; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator; potentiator; corrector},
	year = {2023},
	eissn = {1873-5010},
	pages = {S5-S11}
}

@article{MTMT:33808249,
	title = {Real-time observation of functional specialization among phosphorylation sites in CFTR},
	url = {https://m2.mtmt.hu/api/publication/33808249},
	author = {Infield, D.T. and Schene, M.E. and Fazan, F.S. and Galles, G.D. and Galpin, J.D. and Ahern, C.A.},
	doi = {10.1085/jgp.202213216},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {155},
	unique-id = {33808249},
	issn = {0022-1295},
	year = {2023},
	eissn = {1540-7748}
}

@article{MTMT:33901803,
	title = {Skin-Interfaced Wearable Sweat Sensors for Precision Medicine},
	url = {https://m2.mtmt.hu/api/publication/33901803},
	author = {Min, Jihong and Tu, Jiaobing and Xu, Changhao and Lukas, Heather and Shin, Soyoung and Yang, Yiran and Solomon, Samuel A. and Mukasa, Daniel and Gao, Wei},
	doi = {10.1021/acs.chemrev.2c00823},
	journal-iso = {CHEM REV},
	journal = {CHEMICAL REVIEWS},
	volume = {123},
	unique-id = {33901803},
	issn = {0009-2665},
	abstract = {Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, materials science, and electrochemistry have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extraction and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clinical value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiology of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Additionally, design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extraction to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.},
	year = {2023},
	eissn = {1520-6890},
	pages = {5049-5138},
	orcid-numbers = {Min, Jihong/0000-0002-5788-1473; Xu, Changhao/0000-0002-6817-3341; Yang, Yiran/0000-0001-8770-8746; Gao, Wei/0000-0002-8503-4562}
}

@article{MTMT:34120851,
	title = {It Takes Two to Tango! Protein–Protein Interactions behind cAMP-Mediated CFTR Regulation},
	url = {https://m2.mtmt.hu/api/publication/34120851},
	author = {Murabito, A. and Bhatt, J. and Ghigo, A.},
	doi = {10.3390/ijms241310538},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34120851},
	issn = {1661-6596},
	abstract = {Over the last fifteen years, with the approval of the first molecular treatments, a breakthrough era has begun for patients with cystic fibrosis (CF), the rare genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These molecules, known as CFTR modulators, have led to unprecedented improvements in the lung function and quality of life of most CF patients. However, the efficacy of these drugs is still suboptimal, and the clinical response is highly variable even among individuals bearing the same mutation. Furthermore, not all patients carrying rare CFTR mutations are eligible for CFTR modulator therapies, indicating the need for alternative and/or add-on therapeutic approaches. Because the second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) represents the primary trigger for CFTR activation and a major regulator of different steps of the life cycle of the channel, there is growing interest in devising ways to fine-tune the cAMP signaling pathway for therapeutic purposes. This review article summarizes current knowledge regarding the role of cAMP signalosomes, i.e., multiprotein complexes bringing together key enzymes of the cAMP pathway, in the regulation of CFTR function, and discusses how modulating this signaling cascade could be leveraged for therapeutic intervention in CF. © 2023 by the authors.},
	keywords = {Humans; MUTATION; MUTATION; metabolism; GENETICS; signal transduction; signal transduction; human; Quality of Life; Quality of Life; cyclic AMP; cyclic AMP; CFTR; cystic fibrosis; cystic fibrosis; CFTR protein, human; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis Transmembrane Conductance Regulator; cAMP signaling; CFTR interactors},
	year = {2023},
	eissn = {1422-0067}
}

@article{MTMT:33687604,
	title = {Cystic fibrosis and primary ciliary dyskinesia: Similarities and differences},
	url = {https://m2.mtmt.hu/api/publication/33687604},
	author = {Pereira, R. and Barbosa, T. and Cardoso, A.L. and Sá, R. and Sousa, M.},
	doi = {10.1016/j.rmed.2023.107169},
	journal-iso = {RESP MED},
	journal = {RESPIRATORY MEDICINE},
	volume = {209},
	unique-id = {33687604},
	issn = {0954-6111},
	abstract = {Cystic fibrosis (CF) and Primary ciliary dyskinesia (PCD) are both rare chronic diseases, inherited disorders associated with multiple complications, namely respiratory complications, due to impaired mucociliary clearance that affect severely patients’ lives. Although both are classified as rare diseases, PCD has a much lower prevalence than CF, particularly among Caucasians. As a result, CF is well studied, better recognized by clinicians, and with some therapeutic approaches already available. Whereas PCD is still largely unknown, and thus the approach is based on consensus guidelines, expert opinion, and extrapolation from the larger evidence base available for patients with CF. Both diseases have some clinical similarities but are very different, necessitating different treatment by specialists who are familiar with the complexities of each disease.This review aims to provide an overview of the knowledge about the two diseases with a focus on the similarities and differences between both in terms of disease mechanisms, common clinical manifestations, genetics and the most relevant therapeutic options. We hoped to raise clinical awareness about PCD, what it is, how it differs from CF, and how much information is still lacking. Furthermore, this review emphasises the fact that both diseases require ongoing research to find better treatments and, in particular for PCD, to fill the medical and scientific gaps. © 2023 The Authors},
	keywords = {Rare Diseases; Mucociliary clearance; cystic fibrosis (CF); clinical awareness; Primary ciliary dyskinesia (PCD)},
	year = {2023},
	eissn = {1532-3064}
}

@article{MTMT:33636409,
	title = {Optimization of CFTR gating through the evolution of its extracellular loops},
	url = {https://m2.mtmt.hu/api/publication/33636409},
	author = {Simon, Márton and Csanády, László},
	doi = {10.1085/jgp.202213264},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {155},
	unique-id = {33636409},
	issn = {0022-1295},
	year = {2023},
	eissn = {1540-7748},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@{MTMT:34171345,
	title = {Cystic Fibrosis and the CFTR Anion Channels},
	url = {https://m2.mtmt.hu/api/publication/34171345},
	author = {Yeh, H.-I. and Hwang, T.-C.},
	booktitle = {Textbook of Ion Channels Volume III: Regulation, Physiology, and Diseases},
	doi = {10.1201/9781003310310-10},
	volume = {3},
	unique-id = {34171345},
	abstract = {Cystic fibrosis transmembrane conductance regulator (CFTR), an odd offspring of the ATP-binding cassette (ABC) transporter superfamily, plays a major role in modulating transepithelial water and salt movements in epithelia-lining organs such as the airways and the gastrointestinal tract. Hyperactivation of CFTR causes secretory diarrhea, whereas loss of CFTR function leads to severe damage to the lung in patients with the genetic disease cystic fibrosis. Decades of research on this chloride channel protein is propelled by both its clinical significance and its unique position at the evolutionary crossroads of ion channels and active transporters. Here, we strive to give readers a broad coverage of the structure–function relationships of CFTR with an emphasis on the phosphorylation-dependent activation of its function, and the structural mechanisms for gating and permeation of an activated CFTR. The chapter highlights the recent breakthroughs in the determination of CFTR’s cryo-EM structures, and discusses a number of unresolved controversies and unanswered questions. The chapter ends with a glance over the molecular mechanism underpinning pathogenic mutations in CFTR and the pharmacology of CFTR modulators, areas that not only hold the promise for an ultimate cure for cystic fibrosis but also shed light on the fundamental mechanisms of CFTR function. © 2023 selection and editorial matter, Jie Zheng and Matthew C. Trudeau.},
	year = {2023},
	pages = {173-188}
}

@article{MTMT:33629018,
	title = {Molecular dynamics study of Cl− permeation through cystic fibrosis transmembrane conductance regulator (CFTR)},
	url = {https://m2.mtmt.hu/api/publication/33629018},
	author = {Zeng, Z.W. and Linsdell, P. and Pomès, R.},
	doi = {10.1007/s00018-022-04621-7},
	journal-iso = {CELL MOL LIFE SCI},
	journal = {CELLULAR AND MOLECULAR LIFE SCIENCES},
	volume = {80},
	unique-id = {33629018},
	issn = {1420-682X},
	abstract = {The recent elucidation of atomistic structures of Cl− channel CFTR provides opportunities for understanding the molecular basis of cystic fibrosis. Despite having been activated through phosphorylation and provided with ATP ligands, several near-atomistic cryo-EM structures of CFTR are in a closed state, as inferred from the lack of a continuous passage through a hydrophobic bottleneck region located in the extracellular portion of the pore. Here, we present repeated, microsecond-long molecular dynamics simulations of human CFTR solvated in a lipid bilayer and aqueous NaCl. At equilibrium, Cl− ions enter the channel through a lateral intracellular portal and bind to two distinct cationic sites inside the channel pore but do not traverse the narrow, de-wetted bottleneck. Simulations conducted in the presence of a strong hyperpolarizing electric field led to spontaneous Cl− translocation events through the bottleneck region of the channel, suggesting that the protein relaxed to a functionally open state. Conformational changes of small magnitude involving transmembrane helices 1 and 6 preceded ion permeation through diverging exit routes at the extracellular end of the pore. The pore bottleneck undergoes wetting prior to Cl− translocation, suggesting that it acts as a hydrophobic gate. Although permeating Cl− ions remain mostly hydrated, partial dehydration occurs at the binding sites and in the bottleneck. The observed Cl− pathway is largely consistent with the loci of mutations that alter channel conductance, anion binding, and ion selectivity, supporting the model of the open state of CFTR obtained in the present study. © 2023, The Author(s).},
	keywords = {MOLECULAR MECHANISM; membrane protein; PROTEIN DYNAMICS; ATP-binding cassette; Ion solvation; Pore hydration},
	year = {2023},
	eissn = {1420-9071}
}

@article{MTMT:33176930,
	title = {Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters},
	url = {https://m2.mtmt.hu/api/publication/33176930},
	author = {Chevalier, Benoit and Baatallah, Nesrine and Najm, Matthieu and Castanier, Solene and Jung, Vincent and Pranke, Iwona and Golec, Anita and Stoven, Veronique and Marullo, Stefano and Antigny, Fabrice and Guerrera, Ida Chiara and Sermet-Gaudelus, Isabelle and Edelman, Aleksander and Hinzpeter, Alexandre},
	doi = {10.3390/ijms23168937},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {33176930},
	issn = {1661-6596},
	abstract = {Proteins interacting with CFTR and its mutants have been intensively studied using different experimental approaches. These studies provided information on the cellular processes leading to proper protein folding, routing to the plasma membrane, recycling, activation and degradation. Recently, new approaches have been developed based on the proximity labeling of protein partners or proteins in close vicinity and their subsequent identification by mass spectrometry. In this study, we evaluated TurboID- and APEX2-based proximity labeling of WT CFTR and compared the obtained data to those reported in databases. The CFTR-WT interactome was then compared to that of two CFTR (G551D and W1282X) mutants and the structurally unrelated potassium channel KCNK3. The two proximity labeling approaches identified both known and additional CFTR protein partners, including multiple SLC transporters. Proximity labeling approaches provided a more comprehensive picture of the CFTR interactome and improved our knowledge of the CFTR environment.},
	keywords = {CFTR; cystic fibrosis; interactome; SLC transporters; KCNK3; proximity labeling},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Jung, Vincent/0000-0003-0530-1737; Marullo, Stefano/0000-0001-9604-9973; Antigny, Fabrice/0000-0002-9515-6571}
}

@article{MTMT:33637315,
	title = {The human ATP-binding cassette (ABC) transporter superfamily},
	url = {https://m2.mtmt.hu/api/publication/33637315},
	author = {Dean, M. and Moitra, K. and Allikmets, R.},
	doi = {10.1002/humu.24418},
	journal-iso = {HUM MUTAT},
	journal = {HUMAN MUTATION},
	volume = {43},
	unique-id = {33637315},
	issn = {1059-7794},
	abstract = {The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra- and intracellular membranes. Mutations in ABC genes cause 21 human disorders or phenotypes with Mendelian inheritance, including cystic fibrosis, adrenoleukodystrophy, retinal degeneration, cholesterol, and bile transport defects. To provide tools to study the function of human ABC transporters we compiled data from multiple genomics databases. We analyzed ABC gene conservation within human populations and across vertebrates and surveyed phenotypes of ABC gene mutations in mice. Most mouse ABC gene disruption mutations have a phenotype that mimics human disease, indicating they are applicable models. Interestingly, several ABCA family genes, whose human function is unknown, have cholesterol level phenotypes in the mouse. Genome-wide association studies confirm and extend ABC traits and suggest several new functions to investigate. Whole-exome sequencing of tumors from diverse cancer types demonstrates that mutations in ABC genes are not common in cancer, but specific genes are overexpressed in select tumor types. Finally, an analysis of the frequency of loss-of-function mutations demonstrates that many human ABC genes are essential with a low level of variants, while others have a higher level of genetic diversity. © 2022 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.},
	keywords = {Animals; Humans; MICE; PHENOTYPE; GENETICS; EVOLUTION; EVOLUTION; MOUSE; GENOMICS; review; human; diabetes mellitus; animal; Genetic variability; gene frequency; ATP-Binding Cassette Transporters; gene mutation; HYPERTENSION; nonhuman; hypoglycemia; Genetic Variation; PROTEIN FUNCTION; cholesterol; cholesterol; cholesterol; high density lipoprotein cholesterol; Adenosine Triphosphate; Adenosine Triphosphate; low density lipoprotein cholesterol; ATAXIA; infertility; bile; CARCINOGENESIS; Vertebrates; retinitis pigmentosa; congestive cardiomyopathy; ABC transporter; ABC transporter; genetic conservation; retina degeneration; pseudoxanthoma elasticum; loss of function mutation; bilirubin; cystic fibrosis; gene overexpression; xenobiotic agent; Genome-Wide Association Study; Genome-Wide Association Study; Genome-Wide Association Study; uric acid; hypertrichosis; gene disruption; Human disease; intrahepatic cholestasis; HYPERINSULINEMIA; ichthyosis; human genome; vertebrate; somatic mutation; bile salt; lipid transport; lipid transport; artery calcification; bile acid synthesis; sideroblastic anemia; homocystinuria; Whole exome sequencing; coloboma; malignant neoplasm; methylmalonic aciduria; Adrenoleukodystrophy; monogenic disorder; cholesterol level; Stargardt disease; high density lipoprotein cholesterol level; ATP-binding cassette transporter; Tangier disease; Chondrodysplasia; sitosterolemia; microphthalmia; retina dystrophy; Hypoalphalipoproteinemia; Mendelian inheritance; Dubin Johnson syndrome; neonatal respiratory failure; BARE LYMPHOCYTE SYNDROME},
	year = {2022},
	eissn = {1098-1004},
	pages = {1162-1182}
}

@misc{MTMT:34506610,
	title = {Investigating TRPV4 Signaling in Choroid Plexus Culture Models},
	url = {https://m2.mtmt.hu/api/publication/34506610},
	author = {Hulme, Louise},
	unique-id = {34506610},
	year = {2022}
}

@article{MTMT:32111897,
	title = {CFTR-mediated anion secretion in parathyroid hormone-treated Caco-2 cells is associated with PKA and PI3K phosphorylation but not intracellular pH changes or Na+/K+-ATPase abundance},
	url = {https://m2.mtmt.hu/api/publication/32111897},
	author = {Chaimana, R. and Teerapornpuntakit, J. and Jantarajit, W. and Lertsuwan, K. and Krungchanuchat, S. and Panupinthu, N. and Krishnamra, N. and Charoenphandhu, N.},
	doi = {10.1016/j.bbrep.2021.101054},
	journal-iso = {BIOCHEM BIOPHYS REP},
	journal = {BIOCHEMISTRY AND BIOPHYSICS REPORTS},
	volume = {27},
	unique-id = {32111897},
	year = {2021},
	eissn = {2405-5808}
}

@article{MTMT:32111898,
	title = {Role of Protein Kinase A-Mediated Phosphorylation in CFTR Channel Activity Regulation},
	url = {https://m2.mtmt.hu/api/publication/32111898},
	author = {Della, Sala A. and Prono, G. and Hirsch, E. and Ghigo, A.},
	doi = {10.3389/fphys.2021.690247},
	journal-iso = {FRONT PHYSIOL},
	journal = {FRONTIERS IN PHYSIOLOGY},
	volume = {12},
	unique-id = {32111898},
	year = {2021},
	eissn = {1664-042X}
}

@article{MTMT:32691978,
	title = {The molecular evolution of function in the CFTR chloride channel},
	url = {https://m2.mtmt.hu/api/publication/32691978},
	author = {Infield, Daniel T. and Strickland, Kerry M. and Gaggar, Amit and McCarty, Nael A.},
	doi = {10.1085/jgp.202012625},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {153},
	unique-id = {32691978},
	issn = {0022-1295},
	abstract = {Features of related ABC proteins provided a unique opportunity for emergence of novel channel function in CFTR by incremental evolution. The ATP-binding cassette (ABC) transporter superfamily includes many proteins of clinical relevance, with genes expressed in all domains of life. Although most members use the energy of ATP binding and hydrolysis to accomplish the active import or export of various substrates across membranes, the cystic fibrosis transmembrane conductance regulator (CFTR) is the only known animal ABC transporter that functions primarily as an ion channel. Defects in CFTR, which is closely related to ABCC subfamily members that bear function as bona fide transporters, underlie the lethal genetic disease cystic fibrosis. This article seeks to integrate structural, functional, and genomic data to begin to answer the critical question of how the function of CFTR evolved to exhibit regulated channel activity. We highlight several examples wherein preexisting features in ABCC transporters were functionally leveraged as is, or altered by molecular evolution, to ultimately support channel function. This includes features that may underlie (1) construction of an anionic channel pore from an anionic substrate transport pathway, (2) establishment and tuning of phosphoregulation, and (3) optimization of channel function by specialized ligand-channel interactions. We also discuss how divergence and conservation may help elucidate the pharmacology of important CFTR modulators.},
	keywords = {TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; Nucleotide-binding domain; GENOME PROVIDES INSIGHTS; DEPENDENT HCO3-TRANSPORT; CHARGED AMINO-ACIDS; RESISTANCE PROTEIN MRP1; EXTRACELLULAR LOOP 1; WALKER-B MOTIF},
	year = {2021},
	eissn = {1540-7748}
}

@article{MTMT:32274498,
	title = {Functional stability of CFTR depends on tight binding of ATP at its degenerate ATP-binding site},
	url = {https://m2.mtmt.hu/api/publication/32274498},
	author = {Yeh, Han- I and Yu, Ying-Chun and Kuo, Pei-Lun and Tsai, Chun-Kuang and Huang, Hsin-Tuan and Hwang, Tzyh-Chang},
	doi = {10.1113/JP281933},
	journal-iso = {J PHYSIOL-LONDON},
	journal = {JOURNAL OF PHYSIOLOGY-LONDON},
	volume = {599},
	unique-id = {32274498},
	issn = {0022-3751},
	abstract = {Opening of the cystic fibrosis transmembrane conductance regulator (CFTR) channel is coupled to the motion of its two nucleotide-binding domains: they form a heterodimer sandwiching two functionally distinct ATP-binding sites (sites 1 and 2). While active ATP hydrolysis in site 2 triggers rapid channel closure, the functional role of stable ATP binding in the catalysis-incompetent (or degenerate) site 1, a feature conserved in many other ATP-binding cassette (ABC) transporter proteins, remains elusive. Here, we found that CFTR loses its prompt responsiveness to ATP after the channel is devoid of ATP for tens to hundreds of seconds. Mutants with weakened ATP binding in site 1 and the most prevalent disease-causing mutation, F508del, are more vulnerable to ATP depletion. In contrast, strengthening ligand binding in site 1 with N-6-(2-phenylethyl)-ATP, a high-affinity ATP analogue, or abolishing ATP hydrolysis in site 2 by the mutation D1370N, helps sustain a durable function of the otherwise unstable mutant channels. Thus, tight binding of ATP in the degenerate ATP-binding site is crucial to the functional stability of CFTR. Small molecules targeting site 1 may bear therapeutic potential to overcome the membrane instability of F508del-CFTR.},
	keywords = {ABC transporter; ATP HYDROLYSIS; cystic fibrosis; anion channel; gating},
	year = {2021},
	eissn = {1469-7793},
	pages = {4625-4642},
	orcid-numbers = {Hwang, Tzyh-Chang/0000-0002-1967-8167}
}

@article{MTMT:32628184,
	title = {Arecoline Enhances Phosphodiesterase 4A Activity to Promote Transforming Growth Factor-β-Induced Buccal Mucosal Fibroblast Activation via cAMP-Epac1 Signaling Pathway},
	url = {https://m2.mtmt.hu/api/publication/32628184},
	author = {Zhang, B. and Gao, L. and Shao, C. and Deng, M. and Chen, L.},
	doi = {10.3389/fphar.2021.722040},
	journal-iso = {FRONT PHARMACOL},
	journal = {FRONTIERS IN PHARMACOLOGY},
	volume = {12},
	unique-id = {32628184},
	abstract = {Chewing areca nut (betel quid) is strongly associated with oral submucous fibrosis (OSF), a pre-cancerous lesion. Among the areca alkaloids, arecoline is the main agent responsible for fibroblast proliferation; however, the specific molecular mechanism of arecoline affecting the OSF remains unclear. The present study revealed that arecoline treatment significantly enhanced Transforming growth factor-β (TGF-β)-induced buccal mucosal fibroblast (BMF) activation and fibrotic changes. Arecoline interacts with phosphodiesterase 4A (PDE4A) to exert its effects through modulating PDE4A activity but not PDE4A expression. PDE4A silence reversed the effects of arecoline on TGF-β-induced BMFs activation and fibrotic changes. Moreover, the exchange protein directly activated by cAMP 1 (Epac1)-selective Cyclic adenosine 3′,5′-monophosphate (cAMP) analog (8-Me-cAMP) but not the protein kinase A (PKA)-selective cAMP analog (N6-cAMP) remarkably suppressed α-smooth muscle actin(α-SMA) and Collagen Type I Alpha 1 Chain (Col1A1) protein levels in response to TGF-β1 and arecoline co-treatment, indicating that cAMP-Epac1 but not cAMP-PKA signaling is involved in arecoline functions on TGF-β1-induced BMFs activation. In conclusion, arecoline promotes TGF-β1-induced BMFs activation through enhancing PDE4A activity and the cAMP-Epac1 signaling pathway during OSF. This novel mechanism might provide more powerful strategies for OSF treatment, requiring further in vivo and clinical investigation. © Copyright © 2021 Zhang, Gao, Shao, Deng and Chen.},
	keywords = {arecoline; oral submucous fibrosis; buccal mucosal fibroblast; cAMP-Epac1 signaling pathway; PDE4A},
	year = {2021},
	eissn = {1663-9812}
}