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- Title
SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain.
- Authors
Walker, Michael P.; Rajendra, T.K.; Saieva, Luciano; Fuentes, Jennifer L.; Pellizzoni, Livio; Matera, A. Gregory
- Abstract
Spinal muscular atrophy (SMA) is a recessive neuromuscular disease caused by mutations in the human survival motor neuron 1 (SMN1) gene. The human SMN protein is part of a large macromolecular complex involved in the biogenesis of small ribonucleoproteins. Previously, we showed that SMN is a sarcomeric protein in flies and mice. In this report, we show that the entire mouse Smn complex localizes to the sarcomeric Z-disc. Smn colocalizes with α-actinin, a Z-disc marker protein, in both skeletal and cardiac myofibrils. Furthermore, this localization is both calcium- and calpain-dependent. Calpains are known to release proteins from various regions of the sarcomere as a part of the normal functioning of the muscle; however, this removal can be either direct or indirect. Using mammalian cell lysates, purified native SMN complexes, as well as recombinant SMN protein, we show that SMN is a direct target of calpain cleavage. Finally, myofibers from a mouse model of severe SMA, but not controls, display morphological defects that are consistent with a Z-disc deficiency. These results support the view that the SMN complex performs a muscle-specific function at the Z-discs.
- Publication
Human Molecular Genetics, 2008, Vol 17, Issue 21, p3399
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/ddn234