title: Cannabinoid-induced actomyosin contractility shapes neuronal morphology and growth.
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 sub-ventricular 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 the brain architecture and wiring.
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Alexandre B
authors.initials: AB
authors.lastname: Roland
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Ricobaraza
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Carrel
authors.affiliation: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Jordan
authors.affiliation: U1006 INSERM, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors.forename: Felix
authors.initials: F
authors.lastname: Rico
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Humbert-Claude
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ferrier
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Maureen H
authors.initials: MH
authors.lastname: McFadden
authors.affiliation: U1006 INSERM, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Scheuring
authors.affiliation: Brain Plasticity Unit, ESPCI-ParisTech, CNRS UMR8249, Paris, France.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lenkei
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D024462:Myosin Type II / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D000205:Actomyosin; D054460:rho-Associated Kinases; D024462:Myosin Type II; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein
keywords: RhoA; axon; cannabis; cytoskeleton; dendrite; developmental biology; myosin; neuroscience; rat; stem cells