1. Developmental Biology
  2. Neuroscience
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Cannabinoid-induced actomyosin contractility shapes neuronal morphology and growth

  1. Alexandre B Roland
  2. Ana Ricobaraza
  3. Damien Carrel
  4. Benjamin M Jordan
  5. Felix Rico
  6. Anne C Simon
  7. Marie Humbert-Claude
  8. Jeremy Ferrier
  9. Maureen H McFadden
  10. Simon Scheuring
  11. Zsolt Lenkei  Is a corresponding author
  1. ESPCI-ParisTech, France
  2. Université Paris Descartes, Sorbonne Paris Cité, France
  3. Harvard University, United States
  4. Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, France
Research Article
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Cite this article as: eLife 2014;3:e03159 doi: 10.7554/eLife.03159

Abstract

Endocannabinoids are recently recognized regulators of brain development, but molecular effectors downstream of type-1 cannabinoid receptor (CB1R) activation remain incompletely understood. We report atypical coupling of neuronal CB1Rs, after activation by endo- or exocannabinoids such as the marijuana component ∆9-tetrahydrocannabinol, to heterotrimeric G12/G13 proteins that triggers rapid and reversible non-muscle myosin II (NM II) dependent contraction of the actomyosin cytoskeleton, through a Rho-GTPase and Rho-associated kinase (ROCK). This induces rapid neuronal remodeling, such as retraction of neurites and axonal growth cones, elevated neuronal rigidity and reshaping of somatodendritic morphology. Chronic pharmacological inhibition of NM II prevents cannabinoid-induced reduction of dendritic development in vitro and leads, similarly to blockade of endocannabinoid action, to excessive growth of corticofugal axons into the subventricular zone in vivo. Our results suggest that CB1R can rapidly transform the neuronal cytoskeleton through actomyosin contractility, resulting in cellular remodeling events ultimately able to affect brain architecture and wiring.

Article and author information

Author details

  1. Alexandre B Roland

    ESPCI-ParisTech, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Ana Ricobaraza

    ESPCI-ParisTech, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Damien Carrel

    Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Benjamin M Jordan

    Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Felix Rico

    Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Anne C Simon

    ESPCI-ParisTech, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Marie Humbert-Claude

    ESPCI-ParisTech, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Jeremy Ferrier

    ESPCI-ParisTech, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Maureen H McFadden

    ESPCI-ParisTech, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Simon Scheuring

    Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Zsolt Lenkei

    ESPCI-ParisTech, Paris, France
    For correspondence
    zsolt.lenkei@espci.fr
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Experiments were performed in agreement with the institutional guidelines for the use and care of animals and in compliance with national and international laws and policies (Council directives no. 87-848, 19 October 1987, Ministère de l'Agriculture et de la Forêt, Service Vétérinaire de la Santé et de la Protection Animale). All surgery was performed under Ketamine/Xylazine anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Franck Polleux, Columbia University, United States

Publication history

  1. Received: April 22, 2014
  2. Accepted: September 9, 2014
  3. Accepted Manuscript published: September 15, 2014 (version 1)
  4. Version of Record published: September 30, 2014 (version 2)

Copyright

© 2014, Roland 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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