title: Extracellular Calcium Has Multiple Targets to Control Cell Proliferation.
abstract: Calcium channels and the two G-protein coupled receptors sensing extracellular calcium, calcium-sensing receptor (CaSR) and GPRC6a, are the two main means by which extracellular calcium can signal to cells and regulate many cellular processes including cell proliferation, migration and invasion of tumoral cells. Many intracellular signaling pathways are sensitive to cytosolic calcium rises and conversely intracellular signaling pathways can modulate calcium channel expression and activity. Calcium channels are undoubtedly involved in the former while the CaSR and GPRC6a are most likely to interfere with the latter. As for neurotransmitters, calcium ions use plasma membrane channels and GPCR to trigger cytosolic free calcium concentration rises and intracellular signaling and regulatory pathways activation. Calcium sensing GPCR, CaSR and GPRC6a, allow a supplemental degree of control and as for metabotropic receptors, they not only modulate calcium channel expression but they may also control calcium-dependent K+ channels. The multiplicity of intracellular signaling pathways involved, their sensitivity to local and global intracellular calcium increase and to CaSR and GPRC6a stimulation, the presence of membrane signalplex, all this confers the cells the plasticity they need to convert the effects of extracellular calcium into complex physiological responses and therefore determine their fate.
authors.affiliation: INSERM U1151, INEM (Institut Necker-Enfants Malades), Faculté de Médecine, Université Paris-Descartes, 14 rue Maria Helena Vieira da Silva, Bâtiment Leriche, Porte 14, Paris, 75014, France. thierry.capiod@inserm.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Capiod
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002453:Cell Cycle; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D044169:Receptors, Calcium-Sensing / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D044169:Receptors, Calcium-Sensing; D002118:Calcium
keywords: Calcium channels; Calcium sensing receptors; Cell proliferation; GPRC6a; Orai; TRPC