1. Neuroscience
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Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity

  1. Joju George
  2. Cary Soares
  3. Audrey Montersino
  4. Jean-Claude Beique
  5. Gareth M Thomas  Is a corresponding author
  1. Indiana University School of Medicine, United States
  2. University of Ottawa, Canada
  3. Temple University School of Medicine, United States
Research Article
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Cite this article as: eLife 2015;4:e06327 doi: 10.7554/eLife.06327

Abstract

Precise regulation of the dendritic spine actin cytoskeleton is critical for neurodevelopment and neuronal plasticity, but how neurons spatially control actin dynamics is not well defined. Here, we identify direct palmitoylation of the actin regulator LIM kinase-1 (LIMK1) as a novel mechanism to control spine-specific actin dynamics. A conserved palmitoyl-motif is necessary and sufficient to target LIMK1 to spines and to anchor LIMK1 in spines. ShRNA knockdown/rescue experiments reveal that LIMK1 palmitoylation is essential for normal spine actin polymerization, for spine-specific structural plasticity and for long-term spine stability. Palmitoylation is critical for LIMK1 function because this modification not only controls LIMK1 targeting, but is also essential for LIMK1 activation by its membrane-localized upstream activator PAK. These novel roles for palmitoylation in the spatial control of actin dynamics and kinase signaling provide new insights into structural plasticity mechanisms and strengthen links between dendritic spine impairments and neuropathological conditions.

Article and author information

Author details

  1. Joju George

    Department of Anatomy and Cell Biology, The Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Cary Soares

    Heart and Stroke Partnership for Stroke Recovery, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Audrey Montersino

    Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jean-Claude Beique

    Heart and Stroke Partnership for Stroke Recovery, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Gareth M Thomas

    Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, United States
    For correspondence
    gareth.thomas@temple.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#3439, #4277) of Temple University School of Medicine.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Publication history

  1. Received: January 4, 2015
  2. Accepted: April 16, 2015
  3. Accepted Manuscript published: April 17, 2015 (version 1)
  4. Accepted Manuscript updated: May 1, 2015 (version 2)
  5. Version of Record published: May 13, 2015 (version 3)

Copyright

© 2015, George et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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