Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis. Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed CHRN almost exclusively at neuromuscular junctions. In agreement with previous findings, this data suggests the existence of a specialized subsynaptic zone that is particularly relevant for CHRN recycling.
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http://dx.doi.org/10.1080/21541248.2017.1324939 | DOI Listing |
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Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
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National Research Council of Italy, Institute of Biochemistry and Cell Biology, 00015, Monterotondo, RM, Italy. Electronic address:
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Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, 41013 Seville, Spain.
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UCIBIO-Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116, Gandra, Portugal.
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Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Charcot first described ALS in 1869, but the specific mechanisms that mediate the disease pathology are still not clear. Intense research efforts have provided insight into unique neuroanatomical regions, specific neuronal populations and genetic associations for ALS and other neurodegenerative diseases; however, the experimental results also suggest a convergence of these events to common toxic pathways. We propose that common toxic pathways can be therapeutically targeted, and this intervention will be effective in slowing progression and improving patient quality of life.
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