title: skNAC depletion stimulates myoblast migration and perturbs sarcomerogenesis by enhancing calpain 1 and 3 activity.
abstract: skNAC (skeletal and heart muscle specific variant of nascent polypeptide-associated complex α) is a skeletal and heart muscle-specific protein known to be involved in the regulation of sarcomerogenesis. The respective mechanism, however, is largely unknown. In the present paper, we demonstrate that skNAC regulates calpain activity. Specifically, we show that inhibition of skNAC gene expression leads to enhanced, and overexpression of the skNAC gene to repressed, activity of calpain 1 and, to a lesser extent, calpain 3 in myoblasts. In skNAC siRNA-treated cells, enhanced calpain activity is associated with increased migration rates, as well as with perturbed sarcomere architecture. Treatment of skNAC-knockdown cells with the calpain inhibitor ALLN (N-acetyl-leucyl-leucyl-norleucinal) reverts both the positive effect on myoblast migration and the negative effect on sarcomere architecture. Taken together, our data suggest that skNAC controls myoblast migration and sarcomere architecture in a calpain-dependent manner.
authors.affiliation: Charité - University Medicine Berlin, Institute of Physiology, Thielallee 71, D-14195 Berlin, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Berkholz
authors.forename: Andreas
authors.initials: A
authors.lastname: Zakrzewicz
authors.forename: Barbara
authors.initials: B
authors.lastname: Munz
mesh_terms: D000818:Animals; D001483:Base Sequence; D002154:Calpain / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics*; D009124:Muscle Proteins / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012518:Sarcomeres
chemical_list: D017931:DNA Primers; D018832:Molecular Chaperones; D009124:Muscle Proteins; C096099:nascent-polypeptide-associated complex; C105884:CAPN3 protein, human; D002154:Calpain