VDR activation of intracellular signaling pathways in skeletal muscle

The purpose of this article is to review the activation of signal transduction pathways in skeletal muscle cells by the hormone 1α,25(OH)2-vitamin D3 [1α,25(OH)2D3], focusing on the role of the vitamin D receptor (VDR). The hormone induces fast, non transcriptional responses, involving stimulation of the transmembrane second messenger systems adenylyl cyclase/cAMP/PKA, PLC/DAG + IP3/PKC, Ca2+ messenger system and MAPK cascades. Short treatment with 1α,25(OH)2D3 induces reverse translocation of the VDR from the nucleus to plasma membranes. Accordingly, a complex is formed in the caveolae between the VDR and TRCP3, integral protein of capacitative Ca2+ entry (CCE), suggesting an association between both proteins and a functional role of the VDR in 1α,25(OH)2D3 activation of CCE. Stimulation of tyrosine phosphorylation cascades by 1α,25(OH)2D3 have demonstrated the formation of complexes between Src and the VDR. Through these mechanisms, 1α,25(OH)2D3 plays an important function in contractility and myogenesis.

► Muscle intracelular signaling through VDR. ► Reverse trafficking of VDR in muscle cells. ► Role of VDR in muscle functions.