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Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors

Developing skeletal myofibers in vertebrates are intrinsically “pre-patterned” for motor nerve innervation. However, the intrinsic factors that regulate muscle pre-patterning remain unknown. Here we show that a functional skeletal muscle dihydropyridine receptor (DHPR, the L-type Ca(2+) channel in m...

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Autores principales: Chen, Fujun, Liu, Yun, Sugiura, Yoshie, Allen, Paul D., Gregg, Ronald G., Lin, Weichun
Formato: Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083454/
https://www.ncbi.nlm.nih.gov/pubmed/21441923
http://dx.doi.org/10.1038/nn.2792
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author Chen, Fujun
Liu, Yun
Sugiura, Yoshie
Allen, Paul D.
Gregg, Ronald G.
Lin, Weichun
author_facet Chen, Fujun
Liu, Yun
Sugiura, Yoshie
Allen, Paul D.
Gregg, Ronald G.
Lin, Weichun
author_sort Chen, Fujun
collection PubMed
description Developing skeletal myofibers in vertebrates are intrinsically “pre-patterned” for motor nerve innervation. However, the intrinsic factors that regulate muscle pre-patterning remain unknown. Here we show that a functional skeletal muscle dihydropyridine receptor (DHPR, the L-type Ca(2+) channel in muscle) is required for muscle pre-patterning during the development of the neuromuscular junction (NMJ). Targeted deletion of the β1 subunit of DHPR (Cacnb1) in mice leads to muscle pre-patterning defects, aberrant innervation and precocious maturation of the NMJ. Reintroducing the Cacnb1 gene into Cacnb1(−/−) muscles reverses the pre-patterning defects and restores normal development of the NMJ. The mechanism by which DHPRs govern muscle pre-patterning is independent of their role in excitation-contraction coupling (E-C coupling), but requires Ca(2+) influx through the L-type Ca(2+) channel. Our findings demonstrate that the skeletal muscle DHPR retrogradely regulates the patterning and formation of the NMJ.
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spelling pubmed-30834542011-11-01 Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors Chen, Fujun Liu, Yun Sugiura, Yoshie Allen, Paul D. Gregg, Ronald G. Lin, Weichun Nat Neurosci Article Developing skeletal myofibers in vertebrates are intrinsically “pre-patterned” for motor nerve innervation. However, the intrinsic factors that regulate muscle pre-patterning remain unknown. Here we show that a functional skeletal muscle dihydropyridine receptor (DHPR, the L-type Ca(2+) channel in muscle) is required for muscle pre-patterning during the development of the neuromuscular junction (NMJ). Targeted deletion of the β1 subunit of DHPR (Cacnb1) in mice leads to muscle pre-patterning defects, aberrant innervation and precocious maturation of the NMJ. Reintroducing the Cacnb1 gene into Cacnb1(−/−) muscles reverses the pre-patterning defects and restores normal development of the NMJ. The mechanism by which DHPRs govern muscle pre-patterning is independent of their role in excitation-contraction coupling (E-C coupling), but requires Ca(2+) influx through the L-type Ca(2+) channel. Our findings demonstrate that the skeletal muscle DHPR retrogradely regulates the patterning and formation of the NMJ. 2011-03-27 2011-05 /pmc/articles/PMC3083454/ /pubmed/21441923 http://dx.doi.org/10.1038/nn.2792 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chen, Fujun
Liu, Yun
Sugiura, Yoshie
Allen, Paul D.
Gregg, Ronald G.
Lin, Weichun
Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors
title Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors
title_full Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors
title_fullStr Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors
title_full_unstemmed Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors
title_short Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors
title_sort neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083454/
https://www.ncbi.nlm.nih.gov/pubmed/21441923
http://dx.doi.org/10.1038/nn.2792
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