The SH3 and cysteine-rich domain 3 (Stac3) gene is important to growth, fiber composition, and calcium release from the sarcoplasmic reticulum in postnatal skeletal muscle

Abstract

BackgroundThe SH3 and cysteine-rich domain 3 (Stac3) gene is specifically expressed in the skeletal muscle. Stac3 knockout mice die perinatally. In this study, we determined the potential role of Stac3 in postnatal skeletal muscle growth, fiber composition, and contraction by generating conditional Stac3 knockout mice.MethodsWe disrupted the Stac3 gene in 4-week-old male mice using the Flp-FRT and tamoxifen-inducible Cre-loxP systems.ResultsRT-qPCR and western blotting analyses of the limb muscles of target mice indicated that nearly all Stac3 mRNA and more than 70 % of STAC3 protein were deleted 4 weeks after tamoxifen injection. Postnatal Stac3 deletion inhibited body and limb muscle mass gains. Histological staining and gene expression analyses revealed that postnatal Stac3 deletion decreased the size of myofibers and increased the percentage of myofibers containing centralized nuclei, with no effect on the total myofiber number. Grip strength and grip time tests indicated that postnatal Stac3 deletion decreased limb muscle strength in mice. Muscle contractile tests revealed that postnatal Stac3 deletion reduced electrostimulation-induced but not the ryanodine receptor agonist caffeine-induced maximal force output in the limb muscles. Calcium imaging analysis of single flexor digitorum brevis myofibers indicated that postnatal Stac3 deletion reduced electrostimulation- but not caffeine-induced calcium release from the sarcoplasmic reticulum.ConclusionsThis study demonstrates that STAC3 is important to myofiber hypertrophy, myofiber-type composition, contraction, and excitation-induced calcium release from the sarcoplasmic reticulum in the postnatal skeletal muscle.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-016-0088-4) contains supplementary material, which is available to authorized users.

Dstac Regulates Excitation-Contraction Coupling in Drosophila Body Wall Muscles

“…Stac3 was identified as a novel adaptor protein that is required for EC coupling in zebrafish skeletal muscle and a missense mutation in STAC3 is causal for the congenital Native American myopathy ( Horstick et al, 2013 ). Stac3 also regulates EC coupling in murine skeletal muscles ( Nelson et al, 2013 ) and murine muscle development ( Ge et al, 2014 ; Cong et al, 2016 ). In zebrafish skeletal muscles Stac3 colocalizes with DHPR and RyR and regulates DHPR levels, stability and functionality, including the voltage response of DHPRs but not trafficking of DHPRs ( Linsley et al, 2017a , b ).…”

Congenital myopathy results from misregulation of a muscle Ca 2+ channel by mutant Stac3

“…Stac3 also regulates hypertrophy and fiber-type composition, and mutations in which it is responsible for impaired contractility in mouse muscles (12). Stac3 is expressed selectively in skeletal muscle, colocalizes and biochemically associates with DHPR and RyR1 at triads, and is required for normal release of Ca 2+ from the SR. Coexpression of Stac3 with DHPR in cultured nonmuscle cell lines promotes the trafficking of the channel to the membrane, suggesting a role for Stac3 in trafficking and/or stabilization of the DHPR in the membrane (13).…”

Changes between longissimus dorsi muscle from donkey, cow, and goat assessed by transcriptomic and proteomic analyses

“…STAC3 mRNA was predominantly expressed in skeletal muscle, and regulated myogenic differentiation and myo brillar assembly [39]. STAC3 knockout mouse was embryonically lethal and the skeletal muscles showed signi cant abnormalities [40,41]. In the analysis of protein-protein interactions for DEGs, PCNA, MRPL2, and NADH dehydrogenase compounds were the key nodes.…”