Language
English
Publication Date
3-1-2024
Journal
The Journal of Physiology
DOI
10.1113/JP285894
PMID
38441922
PMCID
PMC10942750
PubMedCentral® Posted Date
3-5-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Spectrins function together with actin as obligatory subunits of the submembranous cytoskeleton. Spectrins maintain cell shape, resist mechanical forces, and stabilize ion channel and transporter protein complexes through binding to scaffolding proteins. Recently, pathogenic variants of SPTBN4 (β4 spectrin) were reported to cause both neuropathy and myopathy. Although β4 spectrin's role in neurons is mostly understood, its function in skeletal muscle, another excitable tissue subject to large forces, is unknown. Here, using a muscle specific β4 spectrin conditional knockout mouse, we show that β4 spectrin does not contribute to muscle function. In addition, we show β4 spectrin is not present in muscle, indicating the previously reported myopathy associated with pathogenic SPTBN4 variants is neurogenic in origin. More broadly, we show that α2, β1, and β2 spectrins are found in skeletal muscle, with α2 and β1 spectrins being enriched at the postsynaptic neuromuscular junction (NMJ). Surprisingly, using muscle specific conditional knockout mice, we show that loss of α2 and β2 spectrins had no effect on muscle health, function, or the enrichment of β1 spectrin at the NMJ. Muscle specific deletion of β1 spectrin also had no effect on muscle health, but with increasing age resulted in the loss of clustered NMJ Na+ channels. Together our results suggest that muscle β1 spectrin functions independently of an associated α spectrin to maintain Na+ channel clustering at the postsynaptic NMJ. Furthermore, despite repeated exposure to strong forces and in contrast to neurons, muscles do not require spectrin cytoskeletons to maintain cell shape or integrity.
Keywords
Animals, Humans, Mice, Actin Cytoskeleton, Muscle, Skeletal, Muscular Diseases, Neuromuscular Junction, Spectrin, Sodium Channels, cytoskeleton, regeneration, neuromuscular junction, repair, axon injury
Published Open-Access
yes
Recommended Citation
Sert, Ozlem; Ding, Xiaoyun; Zhang, Chuansheng; et al., "Postsynaptic β1 Spectrin Maintains Na+ Channels at the Neuromuscular Junction" (2024). Faculty, Staff and Students Publications. 7276.
https://digitalcommons.library.tmc.edu/baylor_docs/7276
Graphical Abstract