title: Inositol 1,4,5 trisphosphate receptor 1 is a key player of human myoblast differentiation.
abstract: Cytosolic Ca(2+) signals are fundamental for the early and late steps of myoblast differentiation and are, as in many cells, generated by Ca(2+) release from internal stores as well as by plasma membrane Ca(2+) entry. Our recent studies identified the store-operated Ca(2+) channels, Orai1 and TRPC1&C4, as crucial for the early steps of human myogenesis and for the late fusion events. In the present work, we assessed the role of the inositol-1,4,5 tris-phosphate receptor (IP3R) type 1 during human myoblast differentiation. We demonstrated, using siRNA strategy that IP3R1 is required for the expression of muscle-specific transcription factors such as myogenin and MEF2 (myocyte enhancer factor 2), and for the formation of myotubes. The knockdown of IP3R1 strongly reduced endogenous spontaneous Ca(2+) transients, and attenuated store-operated Ca(2+) entry. As well, two Ca(2+)-dependent key enzymes of muscle differentiation, NFAT and CamKII are down-regulated upon siIP3R1 treatment. On the contrary, the overexpression of IP3R1 accelerated myoblasts differentiation. These findings identify Ca(2+) release mediated by IP3R1 as an essential mechanism during the early steps of myoblast differentiation.
authors.affiliation: Department of Basic Neurosciences, Geneva Medical Center, 1, Rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Antigny
authors.affiliation: Department of Basic Neurosciences, Geneva Medical Center, 1, Rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Konig
authors.affiliation: Department of Basic Neurosciences, Geneva Medical Center, 1, Rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bernheim
authors.affiliation: Department of Basic Neurosciences, Geneva Medical Center, 1, Rue Michel Servet, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Geneva Medical Center, 1, Rue Michel Servet, 1211 Geneva 4, Switzerland. Electronic address: maud.frieden@unige.ch.
authors.forename: Maud
authors.initials: M
authors.lastname: Frieden
mesh_terms: D002118:Calcium / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D064326:MEF2 Transcription Factors / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000502:physiology*; D018008:Myogenin / Q000502:physiology; D050778:NFATC Transcription Factors / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D064326:MEF2 Transcription Factors; D018008:Myogenin; D050778:NFATC Transcription Factors; D034741:RNA, Small Interfering; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: Calcium channel; Calcium signaling; Inositol 1,4,5 trisphosphate receptor; Myogenesis; Skeletal muscle