Cannabinoid-induced actomyosin contractility shapes neuronal morphology and growth
| Autor: | Maureen H. McFadden, Benjamin M Jordan, Alexandre B. Roland, Felix Rico, Ana Ricobaraza, Damien Carrel, Anne Simon, Marie Humbert-Claude, Jérémy Ferrier, Simon Scheuring, Zsolt Lenkei |
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| Přispěvatelé: | FAS Center for Systems Biology, Harvard University [Cambridge], Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249) (PdC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Department of Organismic and Evolutionary Biology [Cambridge] (OEB), BIO-AFM-LAB Bio Atomic Force Microscopy Laboratory (Bio-AFM-Lab), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-09-MNPS-0004,CannabinoidRemod,Cannabinoides et remodelage neuronal dans le cerveau adolescent, Association entre anomalies structurales, exposition chronique aux cannabinoides et transition psychotique(2009), Harvard University, Aix-Marseille Université, U1006, MNP : Maladies neurologiques et maladies psychiatriques - Cannabinoides et remodelage neuronal dans le cerveau adolescent, Association entre anomalies structurales, exposition chronique aux cannabinoides et transition psychotique - - CannabinoidRemod2009 - ANR-09-MNPS-0004 - MNP - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
cannabis
RHOA Cannabinoid receptor medicine.medical_treatment myosin Rats Sprague-Dawley Mice 0302 clinical medicine Receptor Cannabinoid CB1 Heterotrimeric G protein rat Biology (General) Cytoskeleton Neurons axon rho-Associated Kinases 0303 health sciences biology General Neuroscience Brain cytoskeleton Actomyosin General Medicine Anatomy 3. Good health Cell biology Actin Cytoskeleton Medicine Female Research Article Neurite QH301-705.5 Science Growth Cones macromolecular substances GTP-Binding Protein alpha Subunits G12-G13 General Biochemistry Genetics and Molecular Biology dendrite Contractility 03 medical and health sciences [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Neurites medicine Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Growth cone Cell Shape Cell Proliferation 030304 developmental biology Myosin Type II General Immunology and Microbiology Cannabinoids RhoA Dendrites Actins Developmental Biology and Stem Cells nervous system biology.protein Cannabinoid rhoA GTP-Binding Protein 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | eLife eLife, eLife Sciences Publication, 2014, 3, pp.e03159. ⟨10.7554/eLife.03159.026⟩ eLife, Vol 3 (2014) eLife, 2014, 3, pp.e03159. ⟨10.7554/eLife.03159.026⟩ |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.03159.026⟩ |
| Popis: | 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. DOI: http://dx.doi.org/10.7554/eLife.03159.001 eLife digest Our brains are full of cells called neurons, which are connected to each other in complex networks that send messages around the brain. The way the neurons connect to each other, known as brain wiring, differs widely between individuals. Moreover, our brain wiring changes in response to our environment and experiences throughout our lives, from developing embryo to old age. One way this happens is through the action of chemicals called cannabinoids. Produced naturally in the body, cannabinoids are also found in the popular recreational drug cannabis that is increasingly being used in medicine to treat chronic pain and other conditions. However, cannabis misuse can have negative side effects on the brain leading to memory loss and mental illness, especially in young people. Cannabinoids can be detected by a group of proteins called cannabinoid receptors, but it is not clear how this leads to changes in brain wiring. Roland et al. now show that detection of cannabinoids by a type-1 cannabinoid receptor triggers a series of events that change how neurons grow and connect with each other. Detection of the cannabinoid by the receptor leads to the activation of an enzyme called ROCK. This, in turn, activates a motor protein called non-muscle myosin II that inhibits the growth of neurons. Roland et al. suggest that this prevents the neurons from reaching their neighbors and forming new connections. Investigating how this works in individuals with medical conditions that alter brain function could help inform us how cannabis could be used more safely. DOI: http://dx.doi.org/10.7554/eLife.03159.002 |
| Databáze: | OpenAIRE |
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