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 1 alpha,25(OH)(2)-vitamin D-3[1 alpha,25(OH)(2)D-3], 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 1 alpha,25(OH)(2)D-3 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 1 alpha,25(OH)(2)D-3 activation of CCE. Stimulation of tyrosine phosphorylation cascades by 1 alpha,25(OH)(2)D-3 have demonstrated the formation of complexes between Src and the VDR. Through these mechanisms, 1 alpha,25(OH)(2)D-3 plays an important function in contractility and myogenesis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.