MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function Journal Article


Authors: Metzger, T.; Gache, V.; Xu, M.; Cadot, B.; Folker, E. S.; Richardson, B. E.; Gomes, E. R.; Baylies, M. K.
Article Title: MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function
Abstract: The basic unit of skeletal muscle in all metazoans is the multinucleate myofibre, within which individual nuclei are regularly positioned. The molecular machinery responsible for myonuclear positioning is not known. Improperly positioned nuclei are a hallmark of numerous diseases of muscle, including centronuclear myopathies, but it is unclear whether correct nuclear positioning is necessary for muscle function. Here we identify the microtubule-associated protein ensconsin (Ens)/microtubule-associated protein7 (MAP7) and kinesin heavy chain (Khc)/Kif5b as essential, evolutionarily conserved regulators of myonuclear positioning in Drosophila and cultured mammalian myotubes. We find that these proteins interact physically and that expression of the Kif5b motor domain fused to the MAP7 microtubule-binding domain rescues nuclear positioning defects in MAP7-depleted cells. This suggests that MAP7 links Kif5b to the microtubule cytoskeleton to promote nuclear positioning. Finally, we show that myonuclear positioning is physiologically important. Drosophila ens mutant larvae have decreased locomotion and incorrect myonuclear positioning, and these phenotypes are rescued by muscle-specific expression of Ens. We conclude that improper nuclear positioning contributes to muscle dysfunction in a cell-autonomous fashion. © 2012 Macmillan Publishers Limited. All rights reserved.
Journal Title: Nature
Volume: 484
Issue: 7392
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2012-03-18
Start Page: 120
End Page: 124
Language: English
DOI: 10.1038/nature10914
PROVIDER: scopus
PMCID: PMC3321085
PUBMED: 22425998
DOI/URL:
Notes: --- - "Export Date: 1 May 2012" - "CODEN: NATUA" - "Source: Scopus"
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MSK Authors
  1. Eric Folker
    8 Folker
  2. Mary K Baylies
    85 Baylies
  3. Mu Xu
    2 Xu