ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity

• Type of Material: Article
• Authors: Jiaping Gu, Emory University; Chi Wai Lee, Emory University; Yanjie Fan, Emory University; Daniel Komlos, Rutgers State Univ; Xin Tang, Penn State University; Chicheng Sun, Penn State University; Kuai Yu, Emory University; Criss Hartzell Jr., Emory University; Gong Chen, Penn State University; James R. Bamburg, Colorado State University; James Zheng, Emory University
• Language: English
• Date: 2010-10-01
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Nature America, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/nn.2634
• Title of Journal or Parent Work: Nature Neuroscience
• ISSN: 1097-6256
• Volume: 13
• Issue: 10
• Start Page: 1208
• End Page: 1215
• Grant/Funding Information: This research is supported by grants from the National Institutes of Health to JQZ (GM083889 GM084363, and HD023315), JRB (NS40371), GC (NS054858), and HCH (EY014852 and GM60448).
• Keywords: Science & Technology; LONG-TERM POTENTIATION; COFILIN; MORPHOLOGY; RECYCLING ENDOSOMES; Life Sciences & Biomedicine; LTP; F-ACTIN; DENDRITIC SPINE MORPHOGENESIS; LIM-KINASE; PHOSPHORYLATION; Neurosciences & Neurology; HIPPOCAMPAL SYNAPSES; Neurosciences
• Research Categories: Chemistry, Biochemistry; Biology, Cell

Abstract

Dendritic spines undergo actin-based growth and shrinkage during synaptic plasticity, in which the actin depolymerizing factor (ADF)/cofilin family of actin-associated proteins are important. Elevated ADF/cofilin activities often lead to reduced spine size and immature spine morphology but can also enhance synaptic potentiation in some cases. Thus, ADF/cofilin may have distinct effects on postsynaptic structure and function. We found that ADF/cofilin-mediated actin dynamics regulated AMPA receptor (AMPAR) trafficking during synaptic potentiation, which was distinct from actin's structural role in spine morphology. Specifically, elevated ADF/cofilin activity markedly enhanced surface addition of AMPARs after chemically induced long-term potentiation (LTP), whereas inhibition of ADF/cofilin abolished AMPAR addition. We found that chemically induced LTP elicited a temporal sequence of ADF/cofilin dephosphorylation and phosphorylation that underlies AMPAR trafficking and spine enlargement. These findings suggest that temporally regulated ADF/cofilin activities function in postsynaptic modifications of receptor number and spine size during synaptic plasticity.