Dual Role of an mps-2/KCNE-Dependent Pathway in Long-Term Memory and Age-Dependent Memory Decline
| Autor: | Bánk G. Fenyves, Dominique J.-F. de Quervain, Kiril Tishinov, Carmen Haab, Attila Stetak, Fabian Peter, Andreas W. Arnold, Andreas Papassotiropoulos, Vaibhav G. Gharat |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Memory Long-Term Repressor CREB General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Memory Disorders biology Voltage-gated ion channel Long-term memory Transmembrane protein Potassium channel Cell biology 030104 developmental biology medicine.anatomical_structure Potassium Channels Voltage-Gated biology.protein Neuron General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Current biology : CB. 31(3) |
| ISSN: | 1879-0445 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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