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

Nature Neuroscience volume 13, pages 1208–1215 (2010)Cite this article

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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.

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Figure 1: Rapid addition of postsynaptic AMPA receptors to spine surface during chemical induction of LTP by TEA.
Figure 2: Long-term potentiation of synaptic function induced by TEA treatment.
Figure 3: Effects of actin drugs on TEA-induced AMPAR insertion.
Figure 4: Effects of Ser3 and pSer3 peptides on TEA-induced GluR1 addition.
Figure 5: Effects of different cofilin mutants on TEA-induced GluR1 addition.
Figure 6: Quantitative analyses of spine size in relation to SEP-GluR1 insertion for neurons expressing both mOrange and SEP-GluR1.
Figure 7: Effects of different cofilin mutants on TEA-induced spine enlargement.
Figure 8: Transient activation of cofilin and increase in actin barbed ends during LTP induction by TEA.

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Acknowledgements

This research was supported by grants from the US National Institutes of Health to J.Q.Z. (GM083889 GM084363, and HD023315), J.R.B. (NS40371), G.C. (NS054858) and H.C.H. (EY014852 and GM60448).

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Author notes

  1. Jiaping Gu, Chi Wai Lee and Yanjie Fan: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Cell Biology and Neurology, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia, USA

    Jiaping Gu, Chi Wai Lee, Yanjie Fan, Kuai Yu, H Criss Hartzell & James Q Zheng

  2. Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA

    Daniel Komlos

  3. Department of Biology, Huck Institutes of Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA

    Xin Tang, Chicheng Sun & Gong Chen

  4. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado, USA

    James R Bamburg

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Contributions

J.G. performed a majority of the experiments on SEP-GluR1 insertion, C.W.L. contributed to the data on actin dynamics and Y.F. investigated cofilin phosphorylation and its contribution to spine size changes. D.K. performed the initial work on SEP-GluR1 imaging and cofilin regulation. X.T., C.S. and G.C. provided a majority of the electrophysiology data. K.Y. and H.C.H. contributed to the electrophysiological recordings on neurons expressing cofilin mutants. J.R.B. provided all of the cofilin reagents and insights into cofilin mechanisms and functions. J.Q.Z. designed, planned and guided the project and contributed to the image analysis.

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Correspondence to James Q Zheng.

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Gu, J., Lee, C., Fan, Y. et al. ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity. Nat Neurosci 13, 1208–1215 (2010). https://doi.org/10.1038/nn.2634

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