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

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.

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.

Metrics

  • 2,745
    views
  • 723
    downloads
  • 50
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Joju George
  2. Cary Soares
  3. Audrey Montersino
  4. Jean-Claude Beique
  5. Gareth M Thomas
(2015)
Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity
eLife 4:e06327.
https://doi.org/10.7554/eLife.06327

Share this article

https://doi.org/10.7554/eLife.06327

Further reading

    1. Neuroscience
    Gáspár Oláh, Rajmund Lákovics ... Gábor Tamás
    Research Article

    Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Axonal and dendritic recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Experimentally-based detailed biophysical models have shown that the key factor responsible for the accelerated EPSP propagation in human cortical dendrites is the large conductance load imposed at the soma by the large basal dendritic tree. Additionally, larger dendritic diameters and differences in cable and ion channel properties in humans contribute to enhanced signal propagation. Our integrative experimental and modeling study provides new insights into the scaling rules that help maintain information processing speed albeit the large and sparse neurons in the human cortex.

    1. Neuroscience
    Zhujun Shao, Mengya Zhang, Qing Yu
    Research Article

    When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.