Dual Role of an mps-2/KCNE-Dependent Pathway in Long-Term Memory and Age-Dependent Memory Decline

Fenyves, B.G. [Fenyves, Bánk (Biológia, Oxyológ...), szerző] Biokémiai és Molekuláris Biológiai Intézet (SE / AOK / I); Molekuláris Biológiai Tanszék (SE / AOK / I / BMBI); Arnold, A.*; Gharat, V.G.*; Haab, C.; Tishinov, K.; Peter, F.; de, Quervain D.; Papassotiropoulos, A.; Stetak, A. ✉

Angol nyelvű Szakcikk (Folyóiratcikk) Tudományos
Megjelent: CURRENT BIOLOGY 0960-9822 1879-0445 31 (3) pp. 527-539.e7 2021
  • SJR Scopus - Agricultural and Biological Sciences (miscellaneous): D1
Azonosítók
Activity-dependent persistent changes in neuronal intrinsic excitability and synaptic strength are underlying learning and memory. Voltage-gated potassium (Kv) channels are potential regulators of memory and may be linked to age-dependent neuronal disfunction. MinK-related peptides (MiRPs) are conserved transmembrane proteins modulating Kv channels; however, their possible role in the regulation of memory and age-dependent memory decline are unknown. Here, we show that, in C. elegans, mps-2 is the sole member of the MiRP family that controls exclusively long-term associative memory (LTAM) in AVA neuron. In addition, we demonstrate that mps-2 also plays a critical role in age-dependent memory decline. In young adult worms, mps-2 is transcriptionally upregulated by CRH-1/cyclic AMP (cAMP)-response-binding protein (CREB) during LTAM, although the mps-2 baseline expression is CREB independent and instead, during aging, relies on nhr-66, which acts as an age-dependent repressor. Deletion of nhr-66 or its binding element in the mps-2 promoter prevents age-dependent transcriptional repression of mps-2 and memory decline. Finally, MPS-2 acts through the modulation of the Kv2.1/KVS-3 and Kv2.2/KVS-4 heteromeric potassium channels. Altogether, we describe a conserved MPS-2/KVS-3/KVS-4 pathway essential for LTAM and also for a programmed control of physiological age-dependent memory decline. © 2020 The Authors Fenyves et al. report a conserved MPS-2/KVS-3/KVS-4 pathway essential for long-term associative memory in C. elegans. Furthermore, MPS-2 controls age-dependent memory decline being the target of a controlled repression mechanism mediated by NHR-66. These results provide a link between a conserved memory pathway and age-dependent memory decline. © 2020 The Authors
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2025-02-16 23:43