VDR activation of intracellular signaling pathways in skeletal muscle

Abstract

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 D(3) [1α,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+IP(3)/PKC, Ca(2+) messenger system and MAPK cascades. Short treatment with 1α,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 Ca(2+) entry (CCE), suggesting an association between both proteins and a functional role of the VDR in 1α,25(OH)(2)D(3) activation of CCE. Stimulation of tyrosine phosphorylation cascades by 1α,25(OH)(2)D(3) have demonstrated the formation of complexes between Src and the VDR. Through these mechanisms, 1α,25(OH)(2)D(3) plays an important function in contractility and myogenesis.