한빛사 논문
Hongik Hwanga,b,c,1, Young-Na Hura,1, Heesung Sohna,d, Jiyeon Seoa,b, Jung-Hwa Honga,e, Eunsil Choa, Yuri Choia, Saebom Leea, Seongeun Songa, A-Ram Leea, Suyeon Kima, Dong-Gyu Joc, Hyewhon Rhimb,f, Mikyoung Parka,f,*
aCenter for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, South Korea
bCenter for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, South Korea
cSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, South Korea
dDepartment of Life Sciences, School of Natural Science, Hanyang University, Seoul 04763, South Korea
eDepartment of Life Sciences, Korea University, Seoul 02841, South Korea
fDepartment of Neuroscience, Korea University of Science and Technology, Daejeon 34113, South Korea
1These authors contributed equally to this work.
*Corresponding author
Abstract
While positive regulators of hippocampal long-term potentiation (LTP) have extensively been investigated, relatively little is known about the inhibitory regulators of LTP. We previously reported that Cyclin Y (CCNY), a member of cyclin family generally known to function in proliferating cells, is a novel postsynaptic protein that serves as a negative regulator of functional LTP. However, whether CCNY plays a role in structural LTP, which is mechanistically linked to functional LTP, and which mechanisms are involved in the CCNY-mediated suppression of LTP at the molecular level remain elusive. Here, we report that CCNY negatively regulates the plasticity-induced changes in spine morphology through the control of actin dynamics. We observed that CCNY directly binds to filamentous actin and interferes with LTP-induced actin polymerization as well as depolymerization by blocking the activation of cofilin, an actin-depolymerizing factor, thus resulting in less plastic spines and the impairment of structural LTP. These data suggest that CCNY acts as an inhibitory regulator for both structural and functional LTP by modulating actin dynamics through the cofilin-actin pathway. Collectively, our findings provide a mechanistic insight into the inhibitory modulation of hippocampal LTP by CCNY, highlighting a novel function of a cyclin family protein in non-proliferating neuronal cells.
Keywords : spine plasticity; structural long-term potentiation; cyclin Y; actin; cofilin
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