Skeletal muscle contractions are regulated by a process called excitation-contraction (EC) coupling and defects in it are associated with numerous human myopathies. Recently, the muscle gene, stac3, was identified as a key regulator of EC coupling and a STAC3 mutation causal for the debilitating Native American myopathy (NAM).

"We now show that Stac3 controls EC coupling by regulating Ca2+ channels in muscles. Both the NAM mutation and a mutation that lead to the loss of Stac3 decrease the amount, organization, stability and voltage sensitivity of the Ca2+channels," says Kuwada.

"Furthermore, we found evidence that the NAM allele of STAC3 is linked to Malignant Hyperthermia, a common pharmacogenic disorder. These findings define critical roles for Stac3 in muscle contraction and human disease."

PNAS 2017 114: E228-E236

Authors: Jeremy W. Linsley, I-Uen Hsu, Linda Groom, Viktor Yarotskyy, Manuela Lavorato, Eric J. Horstick, Drew Linsley, Wenjia Wang, Clara Franzini-Armstrong, Robert T. Dirksen, and John Y. Kuwada