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

Autor:	Le Thanh Lam, Sally L. Shirran, Ian Holt, Heidi R. Fuller, Qiuping Zhang, Glenn E. Morris, Caroline Sewry, Catherine M. Shanahan
Přispěvatelé:	University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	Gene isoform Proteomics Nuclear Envelope 0299 Other Physical Sciences Muscle Fibers Skeletal Neuromuscular Junction Kinesins lcsh:Medicine Nerve Tissue Proteins 0601 Biochemistry and Cell Biology Muscle Development Neuromuscular junction Article 03 medical and health sciences 0302 clinical medicine Microtubule Centromere medicine Animals Humans Protein Isoforms Muscle Skeletal lcsh:Science 030304 developmental biology Cell Nucleus 0303 health sciences Multidisciplinary Nesprin Chemistry Myogenesis Microfilament Proteins lcsh:R Skeletal muscle Gene Expression Regulation Developmental DAS Neuromuscular disease Cell biology Cytoskeletal Proteins medicine.anatomical_structure Differentiation Mutation RC0321 Kinesin lcsh:Q RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry 030217 neurology & neurosurgery
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-50728-6
Popis:	This project was supported by grants from the British Heart Foundation (PG/11/71/29091 and PG/16/68/31991) and the Orthopaedic Institute Ltd., (RJAH Orthopaedic Hospital, Oswestry, UK). 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. Publisher PDF
Databáze:	OpenAIRE
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