Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity

• Type of Material: Article
• Authors: Wenliang Lei, Emory University; Kenneth R. Myers, Emory University; Yanfang Rui, Emory University; Siarhei Hladyshau, Georgia Institute of Technology; Denis Tsygankov, Georgia Institute of Technology; James Zheng, Emory University
• Language: English
• Date: 2017-08-01
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Lei et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1083/jcb.201612042
• Title of Journal or Parent Work: Journal of Cell Biology
• ISSN: 0021-9525
• Volume: 216
• Issue: 8
• Start Page: 2551
• End Page: 2564
• Grant/Funding Information: This project is supported in part by research grants from the National Institutes of Health to J.Q. Zheng (MH104632 and GM083889), a Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship to K.R. Myers (NS092342), and a National Institute of Neurological Disorders and Stroke core facilities grant (P30NS055077) to the Integrated Cellular Imaging Microscopy Core of Emory University.
• Keywords: DYNAMICS; MOTILITY; Science & Technology; MECHANISMS; Life Sciences & Biomedicine; LONG-TERM POTENTIATION; CYTOSKELETON; PROFILIN; Cell Biology; NECK; INHIBITOR; PATHOLOGY; MEMBRANE
• Research Categories: Biology, Cell; Biology, Neuroscience

Abstract

Dendritic spines are small postsynaptic compartments of excitatory synapses in the vertebrate brain that are modified during learning, aging, and neurological disorders. The formation and modification of dendritic spines depend on rapid assembly and dynamic remodeling of the actin cytoskeleton in this highly compartmentalized space, but the precise mechanisms remain to be fully elucidated. In this study, we report that spatiotemporal enrichment of actin monomers (G-actin) in dendritic spines regulates spine development and plasticity. We first show that dendritic spines contain a locally enriched pool of G-actin that can be regulated by synaptic activity. We further find that this G-actin pool functions in spine development and its modification during synaptic plasticity. Mechanistically, the relatively immobile G-actin pool in spines depends on the phosphoinositide PI(3,4,5)P 3 and involves the actin monomer-binding protein profilin. Together, our results have revealed a novel mechanism by which dynamic enrichment of G-actin in spines regulates the actin remodeling underlying synapse development and plasticity.