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Nesprin-1-alpha2 associates with kinesin at myotube outer nuclear membranes, but is restricted to neuromuscular junction nuclei in adult muscle

Holt, I; Fuller, H; Lam, LT; Sewry, CA; Shirran, SL; Zhang, Q; Shanahan, CM; Morris, GE

Nesprin-1-alpha2 associates with kinesin at myotube outer nuclear membranes, but is restricted to neuromuscular junction nuclei in adult muscle Thumbnail


Authors

I Holt

LT Lam

CA Sewry

SL Shirran

Q Zhang

CM Shanahan

GE Morris



Abstract

Nesprins, nuclear envelope spectrin-repeat proteins encoded by the SYNE1 and SYNE2 genes, are involved in localization of nuclei. The short isoform, nesprin-1-alpha2, is required for relocation of the microtubule organizer function from centromeres to the nuclear rim during myogenesis. Using specific antibodies, we now show that both nesprin-1-alpha2 and nesprin-1-giant co-localize with kinesin at the junctions of concatenated nuclei and at the outer poles of nuclear chains in human skeletal myotubes. In adult muscle, nesprin-1-alpha2 was found, together with kinesin, only on nuclei associated with neuromuscular junctions, whereas all adult cardiomyocyte nuclei expressed nesprin-1-alpha2. In a proteomics study, kinesin heavy and light chains were the only significant proteins in myotube extracts pulled down by nesprin-1-alpha2, but not by a mutant lacking the highly-conserved STAR domain (18 amino-acids, including the LEWD motif). The results support a function for nesprin-1- alpha2 in the specific localization of skeletal muscle nuclei mediated by kinesins and suggest that its primary role is at the outer nuclear membrane.

Acceptance Date Oct 2, 2019
Publication Date Sep 3, 2019
Publicly Available Date Mar 28, 2024
Journal Scientific Reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
DOI https://doi.org/10.1038/s41598-019-50728-6
Publisher URL http://doi.org/10.1038/s41598-019-50728-6

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