fnins-12-00402 June 26, 2018 Time: 12:46 # 1 ORIGINAL RESEARCH published: 26 June 2018 doi: 10.3389/fnins.2018.00402 Muscarinic Acetylcholine Type 1 Receptor Activity Constrains Neurite Outgrowth by Inhibiting Microtubule Polymerization and Mitochondrial Trafficking in Adult Sensory Neurons Mohammad G. Sabbir1*, Nigel A. Calcutt2 and Paul Fernyhough1,3 1 Division of Neurodegenerative Disorders, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada, 2 Department of Pathology, University of California, San Diego, San Diego, CA, United States, 3 Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada The muscarinic acetylcholine type 1 receptor (M1R) is a metabotropic G protein-coupled Edited by: receptor. Knockout of M1R or exposure to selective or specific receptor antagonists Roberto Di Maio, elevates neurite outgrowth in adult sensory neurons and is therapeutic in diverse University of Pittsburgh, United States models of peripheral neuropathy. We tested the hypothesis that endogenous M1R Reviewed by: activation constrained neurite outgrowth via a negative impact on the cytoskeleton Roland Brandt, University of Osnabrück, Germany and subsequent mitochondrial trafficking. We overexpressed M1R in primary cultures Rick Dobrowsky, of adult rat sensory neurons and cell lines and studied the physiological and The University of Kansas, United States molecular consequences related to regulation of cytoskeletal/mitochondrial dynamics *Correspondence: and neurite outgrowth. In adult primary neurons, overexpression of M1R caused Mohammad G. Sabbir disruption of the tubulin, but not actin, cytoskeleton and significantly reduced neurite
[email protected] outgrowth. Over-expression of a M1R-DREADD mutant comparatively increased neurite Specialty section: outgrowth suggesting that acetylcholine released from cultured neurons interacts This article was submitted to with M1R to suppress neurite outgrowth.