@article{MTMT:34360373, title = {Adam, amigo, brain, and K channel}, url = {https://m2.mtmt.hu/api/publication/34360373}, author = {Kodirov, Sodikdjon A.}, doi = {10.1007/s12551-023-01163-5}, journal-iso = {BIOPHYSICAL REVIEWS}, journal = {BIOPHYSICAL REVIEWS}, unique-id = {34360373}, issn = {1867-2450}, abstract = {Voltage-dependent K+ (Kv) channels are diverse, comprising the classical Shab - Kv2, Shaker - Kv1, Shal - Kv4, and Shaw - Kv3 families. The Shaker family alone consists of Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv1.6, and Kv1.7. Moreover, the Shab family comprises two functional (Kv2.1 and Kv2.2) and several "silent" alpha subunits (Kv2.3, Kv5, Kv6, Kv8, and Kv9), which do not generate K current. However, e.g., Kv8.1, via heteromerization, inhibits outward currents of the same family or even that of Shaw. This property of Kv8.1 is similar to those of designated beta subunits or non-selective auxiliary elements, including ADAM or AMIGO proteins. Kv channels and, in turn, ADAM may modulate the synaptic long-term potentiation (LTP). Prevailingly, Kv1.1 and Kv1.5 are attributed to respective brain and heart pathologies, some of which may occur simultaneously. The aforementioned channel proteins are apparently involved in several brain pathologies, including schizophrenia and seizures.}, keywords = {INACTIVATION; PATCH-CLAMP; LTP; Kv1; auxiliary subunit; Kv2}, year = {2023}, eissn = {1867-2469} } @article{MTMT:33932520, title = {A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating K(v)1.1}, url = {https://m2.mtmt.hu/api/publication/33932520}, author = {Zhou, Lin and Wang, Kang and Xu, Yuxiang and Dong, Bin-Bin and Wu, Deng-Chang and Wang, Zhao-Xiang and Wang, Xin-Tai and Cai, Xin-Yu and Yang, Jin-Tao and Zheng, Rui and Chen, Wei and Shen, Ying and Wei, Jian-She}, doi = {10.1186/s13578-023-00983-y}, journal-iso = {CELL BIOSCI}, journal = {CELL AND BIOSCIENCE}, volume = {13}, unique-id = {33932520}, abstract = {BackgroundAutosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that functional LGI1 is secreted by excitatory neurons, GABAergic interneurons, and astrocytes, and regulates AMPA-type glutamate receptor-mediated synaptic transmission by binding ADAM22 and ADAM23. However, > 40 LGI1 mutations have been reported in familial ADLTE patients, more than half of which are secretion-defective. How these secretion-defective LGI1 mutations lead to epilepsy is unknown.ResultsWe identified a novel secretion-defective LGI1 mutation from a Chinese ADLTE family, LGI1-W183R. We specifically expressed mutant LGI1(W183R) in excitatory neurons lacking natural LGI1, and found that this mutation downregulated K(v)1.1 activity, led to neuronal hyperexcitability and irregular spiking, and increased epilepsy susceptibility in mice. Further analysis revealed that restoring K(v)1.1 in excitatory neurons rescued the defect of spiking capacity, improved epilepsy susceptibility, and prolonged the life-span of mice.ConclusionsThese results describe a role of secretion-defective LGI1 in maintaining neuronal excitability and reveal a new mechanism in the pathology of LGI1 mutation-related epilepsy.}, keywords = {EPILEPSY; Precision Medicine; leucine-rich glioma inactivated 1; ADLTE}, year = {2023}, eissn = {2045-3701} } @article{MTMT:33688719, title = {A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating Kv1. 1}, url = {https://m2.mtmt.hu/api/publication/33688719}, author = {Zhou, Lin and Wang, Kang and Xu, Yuxiang and Dong, Bin-Bin and Wu, Deng-Chang and Wang, Zhao-Xiang and Wang, Xin-Tai and Cai, Xin-Yu and Yang, Jin-Tao and Zheng, Rui}, journal-iso = {CELL BIOSCI}, journal = {CELL AND BIOSCIENCE}, volume = {13}, unique-id = {33688719}, year = {2023}, eissn = {2045-3701}, pages = {34} } @article{MTMT:33274154, title = {Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?}, url = {https://m2.mtmt.hu/api/publication/33274154}, author = {Kovács, Tamás and Nagy, Péter and Panyi, György and Szente, Lajos and Varga, Zoltán and Zákány, Florina}, doi = {10.3390/pharmaceutics14122559}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {14}, unique-id = {33274154}, issn = {1999-4923}, abstract = {Cyclodextrins, representing a versatile family of cyclic oligosaccharides, have extensive pharmaceutical applications due to their unique truncated cone-shaped structure with a hydrophilic outer surface and a hydrophobic cavity, which enables them to form non-covalent host–guest inclusion complexes in pharmaceutical formulations to enhance the solubility, stability and bioavailability of numerous drug molecules. As a result, cyclodextrins are mostly considered as inert carriers during their medical application, while their ability to interact not only with small molecules but also with lipids and proteins is largely neglected. By forming inclusion complexes with cholesterol, cyclodextrins deplete cholesterol from cellular membranes and thereby influence protein function indirectly through alterations in biophysical properties and lateral heterogeneity of bilayers. In this review, we summarize the general chemical principles of direct cyclodextrin–protein interactions and highlight, through relevant examples, how these interactions can modify protein functions in vivo, which, despite their huge potential, have been completely unexploited in therapy so far. Finally, we give a brief overview of disorders such as Niemann–Pick type C disease, atherosclerosis, Alzheimer’s and Parkinson’s disease, in which cyclodextrins already have or could have the potential to be active therapeutic agents due to their cholesterol-complexing or direct protein-targeting properties.}, year = {2022}, eissn = {1999-4923}, orcid-numbers = {Nagy, Péter/0000-0002-7466-805X; Panyi, György/0000-0001-6227-3301; Szente, Lajos/0000-0002-7734-5440} } @misc{MTMT:33688725, title = {Hinokitiol alters Gene Expression in Aspergillus fumigatus, protects against fungal keratitis by Reducing Fungal Load, LOX-1, Proinflammatory cytokines and Neutrophil Infiltration}, url = {https://m2.mtmt.hu/api/publication/33688725}, author = {Ma, Shuqin and Lin, Hao and Peng, Xudong and Li, Cui and Wang, Qian and Xu, Qiang and He, Mengting and Shao, Dan and Liu, Xing and Zhao, Guiqiu}, unique-id = {33688725}, abstract = {peer review}, year = {2022}, pages = {2022} } @{MTMT:34567593, title = {Potassium and Calcium Channel Complexes as Novel Targets for Cancer Research}, url = {https://m2.mtmt.hu/api/publication/34567593}, author = {Potier-Cartereau, Marie and Raoul, William and Weber, Gunther and Maheo, Karine and Rapetti-Mauss, Raphael and Gueguinou, Maxime and Buscaglia, Paul and Goupille, Caroline and Le, Goux Nelig and Abdoul-Azize, Souleymane and Lecomte, Thierry and Fromont, Gaelle and Chantome, Aurelie and Mignen, Olivier and Soriani, Olivier and Vandier, Christophe}, booktitle = {Targets of Cancer Diagnosis and Treatment}, doi = {10.1007/112_2020_24}, unique-id = {34567593}, abstract = {The intracellular Ca2+ concentration is mainly controlled by Ca2+ channels. These channels form complexes with K+ channels, which function to amplify Ca2+ flux. In cancer cells, voltage-gated/voltage-dependent Ca2+ channels and non-voltage-gated/ voltage-independent Ca2+ channels have been reported to interact with K+ channels such as Ca2+-activated K+ channels and voltage-gated K+ channels. These channels are activated by an increase in cytosolic Ca2+ concentration or by membrane depolarization, which induces membrane hyperpolarization, increasing the driving force for Ca2+ flux. These complexes, composed of K+ and Ca2+ channels, are regulated by several molecules including lipids (ether lipids and cholesterol), proteins (e.g. STIM), receptors (e.g. S1R/SIGMAR1), and peptides (e.g. LL-37) and can be targeted by monoclonal antibodies, making them novel targets for cancer research.}, year = {2022}, pages = {157-176}, orcid-numbers = {Raoul, William/0000-0002-5040-3372; Gueguinou, Maxime/0000-0002-5793-2082; Abdoul-Azize, Souleymane/0000-0003-2065-9091} } @article{MTMT:31996377, title = {Statin‐boosted cellular uptake and endosomal escape of penetratin due to reduced membrane dipole potential}, url = {https://m2.mtmt.hu/api/publication/31996377}, author = {Batta, Gyula Gábor (Ifj.) and Kárpáti, Levente and Henrique, Gabriela Fulaneto and Tóth, Gabriella and Tarapcsák, Szabolcs and Kovács, Tamás and Zákány, Florina and Mándity, István and Nagy, Péter}, doi = {10.1111/bph.15509}, journal-iso = {BR J PHARMACOL}, journal = {BRITISH JOURNAL OF PHARMACOLOGY}, volume = {178}, unique-id = {31996377}, issn = {0007-1188}, year = {2021}, eissn = {1476-5381}, pages = {3667-3681}, orcid-numbers = {Batta, Gyula Gábor (Ifj.)/0000-0001-8735-6920; Kárpáti, Levente/0000-0002-9091-3027; Kovács, Tamás/0000-0002-1084-9847; Mándity, István/0000-0003-2865-6143; Nagy, Péter/0000-0002-7466-805X} } @article{MTMT:32276748, title = {A novel mitochondrial Kv1.3-caveolin axis controls cell survival and apoptosis}, url = {https://m2.mtmt.hu/api/publication/32276748}, author = {Capera, Jesusa and Perez-Verdaguer, Mireia and Peruzzo, Roberta and Navarro-Perez, Maria and Martinez-Pinna, Juan and Alberola-Die, Armando and Morales, Andres and Leanza, Luigi and Szabo, Ildiko and Felipe, Antonio}, doi = {10.7554/eLife.69099}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {10}, unique-id = {32276748}, issn = {2050-084X}, abstract = {The voltage-gated potassium channel Kv1.3 plays an apparent dual physiological role by participating in activation and proliferation of leukocytes as well as promoting apoptosis in several types of tumor cells. Therefore, Kv1.3 is considered a potential pharmacological target for immunodeficiency and cancer. Different cellular locations of Kv1.3, at the plasma membrane or the mitochondria, could be responsible for such duality. While plasma membrane Kv1.3 facilitates proliferation, the mitochondrial channel modulates apoptotic signaling. Several molecular determinants of Kv1.3 drive the channel to the cell surface, but no information is available about its mitochondrial targeting. Caveolins, which are able to modulate cell survival, participate in the plasma membrane targeting of Kv1.3. The channel, via a caveolin-binding domain (CDB), associates with caveolin 1 (Cav1), which localizes Kv1.3 to lipid raft membrane microdomains. The aim of our study was to understand the role of such interactions not only for channel targeting but also for cell survival in mammalian cells. By using a caveolin association-deficient channel (Kv1.3 CDBless), we demonstrate here that while the Kv1.3-Cav1 interaction is responsible for the channel localization in the plasma membrane, a lack of such interaction accumulates Kv1.3 in the mitochondria. Kv1.3 CDBless severely affects mitochondrial physiology and cell survival, indicating that a functional link of Kv1.3 with Cav1 within the mitochondria modulates the pro-apoptotic effects of the channel. Therefore, the balance exerted by these two complementary mechanisms fine-tune the physiological role of Kv1.3 during cell survival or apoptosis. Our data highlight an unexpected role for the mitochondrial caveolin-Kv1.3 axis during cell survival and apoptosis.}, year = {2021}, eissn = {2050-084X}, orcid-numbers = {Capera, Jesusa/0000-0002-8123-7725; Peruzzo, Roberta/0000-0001-9209-9068; Alberola-Die, Armando/0000-0001-5391-5739; Morales, Andres/0000-0002-1526-3327} } @article{MTMT:32510829, title = {Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction}, url = {https://m2.mtmt.hu/api/publication/32510829}, author = {Kovács, Tamás and Sohajda, Tamás and Szente, Lajos and Nagy, Péter and Panyi, György and Varga, Zoltán and Zákány, Florina}, doi = {10.3389/fmolb.2021.735357}, journal-iso = {FRONT MOL BIOSCI}, journal = {FRONTIERS IN MOLECULAR BIOSCIENCES}, volume = {8}, unique-id = {32510829}, year = {2021}, eissn = {2296-889X}, orcid-numbers = {Kovács, Tamás/0000-0002-1084-9847; Nagy, Péter/0000-0002-7466-805X; Panyi, György/0000-0001-6227-3301} } @article{MTMT:32219377, title = {An omega-3, but Not an omega-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin}, url = {https://m2.mtmt.hu/api/publication/32219377}, author = {Zákány, Florina and Szabó, Máté and Batta, Gyula Gábor (Ifj.) and Kárpáti, Levente and Mándity, István and Fülöp, Péter and Varga, Zoltán and Panyi, György and Nagy, Péter and Kovács, Tamás}, doi = {10.3389/fcell.2021.647300}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {9}, unique-id = {32219377}, issn = {2296-634X}, abstract = {Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and omega-6 gamma-linolenic acid (GLA) increase, while omega-3 alpha-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity. Pretreatment with ALA counteracts, while SA or GLA enhances cholesterol-induced DP elevations. Furthermore, ALA (but not SA or GLA) increases endo-lysosomal escape of penetratin, a cell-penetrating peptide. In summary, we have developed a novel method to measure DP in large quantities of individual living cells and propose ALA as a physiological DP lowering agent facilitating cytoplasmic entry of penetratin.}, keywords = {Flow Cytometry; cholesterol; PENETRATIN; Polyunsaturated fatty acids; Membrane dipole potential}, year = {2021}, eissn = {2296-634X}, orcid-numbers = {Batta, Gyula Gábor (Ifj.)/0000-0001-8735-6920; Kárpáti, Levente/0000-0002-9091-3027; Mándity, István/0000-0003-2865-6143; Panyi, György/0000-0001-6227-3301; Nagy, Péter/0000-0002-7466-805X; Kovács, Tamás/0000-0002-1084-9847} } @article{MTMT:31507319, title = {Interfacial Binding Sites for Cholesterol on Kir, Kv, K-2P, and Related Potassium Channels}, url = {https://m2.mtmt.hu/api/publication/31507319}, author = {Lee, Anthony G.}, doi = {10.1016/j.bpj.2020.05.028}, journal-iso = {BIOPHYS J}, journal = {BIOPHYSICAL JOURNAL}, volume = {119}, unique-id = {31507319}, issn = {0006-3495}, abstract = {Inwardly rectifying, voltage-gated, two-pore domain, and related K+ channels are located in eukaryotic membranes rich in cholesterol. Here, molecular docking is used to detect specific binding sites ("hot spots") for cholesterol on K+ channels with characteristics that match those of known cholesterol binding sites. The transmembrane surfaces of all available high-resolution structures for K+ channels were swept for potential binding sites. Cholesterol poses were found to be located largely in hollows between protein ridges. A comparison between cholesterol poses and resolved phospholipids suggests that not all cholesterol molecules binding to the transmembrane surface of a K+ channel will result in displacement of a phospholipid molecule from the surface. Competition between cholesterol binding and binding of anionic phospholipids essential for activity could explain some of the effects of cholesterol on channel function.}, year = {2020}, eissn = {1542-0086}, pages = {35-47} } @article{MTMT:31312818, title = {Direct and indirect cholesterol effects on membrane proteins with special focus on potassium channels}, url = {https://m2.mtmt.hu/api/publication/31312818}, author = {Zákány, Florina and Kovács, Tamás and Panyi, György and Varga, Zoltán}, doi = {10.1016/j.bbalip.2020.158706}, journal-iso = {BBA-MOL CELL BIOL L}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS}, volume = {1865}, unique-id = {31312818}, issn = {1388-1981}, abstract = {As described in the literature the interaction between cholesterol and membrane proteins can occur via direct, ligand-like and indirect mechanisms, in which cholesterol effects are mediated by alterations in the biophysical properties or in the protein-organizing functions of the lipid membrane. Early studies emphasized the importance of indirect and raft-mediated effects, but improvements in computational and structural imaging techniques allowed the definition of a wide range of functionally active cholesterol binding domains and sites suggesting the relevance of direct cholesterol effects in various proteins. However, the intramolecular rearrangements induced by cholesterol leading to modulation of ion channel gating, membrane transport and receptor functions still have not been revealed. In this review we summarize the novel findings of the topic by focusing on recent studies about direct and indirect effects of cholesterol on potassium ion channels, and we extend the review to transporters and receptors with different domain structures to introduce the general mechanisms of cholesterol action among membrane proteins. We propose that rather than pure direct or indirect effects, cholesterol action on membrane proteins can be better described as a mixture of indirect and direct interactions with system-specific variability in their contributions, which can be explored by using a multi-level approach employing multiple experimental techniques. © 2020 The Authors}, keywords = {calcium; RECEPTORS; SODIUM; POTASSIUM; ION CHANNELS; TRANSPORTERS; review; membrane protein; priority journal; biosynthesis; transient receptor potential channel; HYDRATION; PROTEIN FUNCTION; elasticity; cholesterol; cholesterol; ion channel; adenosine triphosphatase (potassium sodium); binding affinity; chemical structure; epidermal growth factor receptor; protein domain; potassium channel; calcium channel; Hydrophobicity; structure analysis; electric potential; dipole; ABC transporter; protein interaction; lipid raft; G protein coupled receptor; protein tyrosine kinase; Membrane transport; protein motif; voltage gated potassium channel; membrane potential; channel gating; chemical stress; potassium conductance; Hedgehog signaling; ligand gated ion channel; Direct cholesterol effects; Indirect cholesterol effects}, year = {2020}, eissn = {1879-2618}, orcid-numbers = {Kovács, Tamás/0000-0002-1084-9847; Panyi, György/0000-0001-6227-3301} } @article{MTMT:30669164, title = {Emerging Diversity in Lipid–Protein Interactions}, url = {https://m2.mtmt.hu/api/publication/30669164}, author = {Corradi, Valentina and Sejdiu, Besian I and Mesa-Galloso, Haydee and Abdizadeh, Haleh and Noskov, Sergei Yu and Marrink, Siewert J and Tieleman, D Peter}, doi = {10.1021/acs.chemrev.8b00451}, journal-iso = {CHEM REV}, journal = {CHEMICAL REVIEWS}, volume = {119}, unique-id = {30669164}, issn = {0009-2665}, year = {2018}, eissn = {1520-6890}, pages = {5775-5848} }