AUTHOR=Hogg David W. , Reid Andrea L. , Dodsworth Thomas L. , Chen Yani , Reid Ross M. , Xu Mei , Husic Mia , Biga Peggy R. , Slee Andrew , Buck Leslie T. , Barsyte-Lovejoy Dalia , Locke Marius , Lovejoy David A. TITLE=Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1 JOURNAL=Frontiers in Physiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1031264 DOI=10.3389/fphys.2022.1031264 ISSN=1664-042X ABSTRACT=

Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca2+ signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.