PMID- 33259792 OWN - NLM STAT- MEDLINE DCOM- 20220103 LR - 20220103 IS - 1879-0445 (Electronic) IS - 0960-9822 (Linking) VI - 31 IP - 3 DP - 2021 Feb 8 TI - Dual Role of an mps-2/KCNE-Dependent Pathway in Long-Term Memory and Age-Dependent Memory Decline. PG - 527-539.e7 LID - S0960-9822(20)31612-2 [pii] LID - 10.1016/j.cub.2020.10.069 [doi] AB - Activity-dependent persistent changes in neuronal intrinsic excitability and synaptic strength are underlying learning and memory. Voltage-gated potassium (K(v)) channels are potential regulators of memory and may be linked to age-dependent neuronal disfunction. MinK-related peptides (MiRPs) are conserved transmembrane proteins modulating K(v) 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 K(v)2.1/KVS-3 and K(v)2.2/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. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Fenyves, Bank G AU - Fenyves BG AD - Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Department of Molecular Biology, Semmelweis University, Tuzolto u. 37-47, 1094 Budapest, Hungary. FAU - Arnold, Andreas AU - Arnold A AD - Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland. FAU - Gharat, Vaibhav G AU - Gharat VG AD - Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland. FAU - Haab, Carmen AU - Haab C AD - Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland. FAU - Tishinov, Kiril AU - Tishinov K AD - Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland. FAU - Peter, Fabian AU - Peter F AD - Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland. FAU - de Quervain, Dominique AU - de Quervain D AD - Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland. FAU - Papassotiropoulos, Andreas AU - Papassotiropoulos A AD - Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Biozentrum, Life Sciences Training Facility, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland. FAU - Stetak, Attila AU - Stetak A AD - Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; University Psychiatric Clinics, University of Basel, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland. Electronic address: a.stetak@unibas.ch. LA - eng GR - P40 OD010440/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201130 PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Potassium Channels, Voltage-Gated) SB - IM MH - Animals MH - Caenorhabditis elegans/genetics/metabolism MH - Caenorhabditis elegans Proteins/genetics/metabolism MH - *Memory Disorders MH - *Memory, Long-Term MH - Potassium Channels, Voltage-Gated OTO - NOTNLM OT - Caenorhabditis elegans OT - KCNE OT - ageing OT - kvs-3 OT - kvs-4 OT - long-term memory OT - mps-2 OT - nhr-66 OT - voltage-gated ion-channel COIS- Declaration of Interests The authors declare no competing interests. EDAT- 2020/12/02 06:00 MHDA- 2022/01/04 06:00 CRDT- 2020/12/01 20:08 PHST- 2020/06/15 00:00 [received] PHST- 2020/09/14 00:00 [revised] PHST- 2020/10/21 00:00 [accepted] PHST- 2020/12/02 06:00 [pubmed] PHST- 2022/01/04 06:00 [medline] PHST- 2020/12/01 20:08 [entrez] AID - S0960-9822(20)31612-2 [pii] AID - 10.1016/j.cub.2020.10.069 [doi] PST - ppublish SO - Curr Biol. 2021 Feb 8;31(3):527-539.e7. doi: 10.1016/j.cub.2020.10.069. Epub 2020 Nov 30.