Control of Skeletal Muscle Cell Growth and Size Through Adhesion GPCRs

Skeletal muscle homeostasis is regulated by a constant influx of chemicals and exposure to mechanical stimuli. A number of key signaling pathways that translate these stimuli into changes in muscle physiology have been established. The GPCR family known as adhesion GPCRs (aGPCRs) has largely elusive roles in skeletal muscle biology; however, their unique capacity to activate adhesion and G protein signaling pathways makes them an attractive point of investigation. The skeletal muscle myofiber contains a highly organized cytoarchitecture to ensure contractile function. This requires intricate interactions with components of the extracellular matrix (ECM) surrounding each fiber. aGPCRs possess extended N-termini known to interact with ECM proteins and complexes suggesting a compatible role in skeletal muscle biology. Furthermore, recent work demonstrated the involvement of certain aGPCRs in whole muscle hypertrophy and differentiation of muscle progenitor cells. Signaling pathways downstream of aGPCRs are still incompletely understood; however, initial findings show involvement of the Gα12/13 subunit signaling to the pro-anabolic Akt/mTOR pathway. Together, this chapter will review the emerging role of aGPCRs in skeletal muscle biology and putative mechanism(s) employed to regulate skeletal muscle growth.