Journal Article

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

Sun, Chicheng, Hartzell, H Criss, Chen, Gong, Tang, Xin, Komlos, Daniel, Zheng, James Q, Lee, Chi Wai, Bamburg, James R, Gu, Jiaping, Fan, Yanjie, Yu, Kuai

2010

Overview

Segregating glutamate receptor trafficking function from the changes in synaptic spine morphology, this study finds that actin depolymerizing factor (ADF)- and cofilin-mediated actin dynamics control AMPAR trafficking during chemically induced long-term potentiation independent of actin's structural role. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/378/1595 / 631/378/2571 / 631/378/2591 / 631/378/548/2590 / Actin / Actin Depolymerizing Factors - genetics / Actin Depolymerizing Factors - physiology / Actins - metabolism / Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological Techniques / Biology / Biomedical and Life Sciences / Biomedicine / Biophysics / Bridged Bicyclo Compounds, Heterocyclic - pharmacology / Cells, Cultured / Cytoskeleton / Dendritic Spines - drug effects / Dendritic Spines - metabolism / Dose-Response Relationship, Drug / Drug Interactions / Electric Stimulation - methods / Embryo, Mammalian / Excitatory Amino Acid Antagonists - pharmacology / Female / Gene Expression Regulation - drug effects / Gene Expression Regulation - genetics / Green Fluorescent Proteins - genetics / Hippocampus - cytology / Humans / Hydrogen-Ion Concentration / Kinases / Long-Term Potentiation - genetics / Long-Term Potentiation - physiology / Luminescent Proteins - genetics / Morphology / Neurobiology / Neurons - cytology / Neurons - physiology / Neurosciences / Neurotransmitters / Patch-Clamp Techniques / Phosphorylation / Phosphorylation - drug effects / Phosphorylation - genetics / Potassium Channel Blockers - pharmacology / Pregnancy / Properties / Protein Transport - genetics / Rats / Receptors, AMPA - genetics / Receptors, AMPA - metabolism / Red Fluorescent Protein / Synapses - genetics / Synapses - physiology / Tetraethylammonium - pharmacology / Thiazolidines - pharmacology / Time Factors / Transfection - methods