We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function.
- Authors
Metzger, Thomas; Gache, Vincent; Xu, Mu; Cadot, Bruno; Folker, Eric S.; Richardson, Brian E.; Gomes, Edgar R.; Baylies, Mary K.
- 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 protein?7 (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.
- Subjects
DROSOPHILA physiology; MICROTUBULE-associated protein kinase; SKELETAL muscle physiology; MUSCLE abnormalities; KINESIN
- Publication
Nature, 2012, Vol 484, Issue 7392, p120
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature10914