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

• 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
• Journal Title: Nature Neuroscience
• Volume: Volume 13, Number 10
• Publisher: Nature Research (part of Springer Nature) | 2010-10-01, Pages 1208-1215
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/nn.2634
• Subjects: Chemistry, Biochemistry; Biology, Cell
• Keywords: Science & Technology; Life Sciences & Biomedicine; Neurosciences; Neurosciences & Neurology; LONG-TERM POTENTIATION; DENDRITIC SPINE MORPHOGENESIS; HIPPOCAMPAL SYNAPSES; RECYCLING ENDOSOMES; LIM-KINASE; F-ACTIN; COFILIN; LTP; PHOSPHORYLATION; MORPHOLOGY

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.