I Holt
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
Authors
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 |
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 |
Files
s41598-019-50728-6.pdf
(4.3 Mb)
PDF
266971_2_merged_1566483138.pdf
(13.1 Mb)
PDF