title: TRPC1 and TRPC4 channels functionally interact with STIM1L to promote myogenesis and maintain fast repetitive Ca2+release in human myotubes.
abstract: STIM1 and Orai1 are essential players of store-operated Ca2+entry (SOCE) in human skeletal muscle cells and are required for adult muscle differentiation. Besides these two proteins, TRPC (transient receptor potential canonical) channels and STIM1L (a longer STIM1 isoform) are also present on muscle cells. In the present study, we assessed the role of TRPC1, TRPC4 and STIM1L in SOCE, in the maintenance of repetitive Ca2+transients and in muscle differentiation. Knockdown of TRPC1 and TRPC4 reduced SOCE by about 50% and significantly delayed the onset of Ca2+entry, both effects similar to STIM1L invalidation. Upon store depletion, TRPC1 and TRPC4 appeared to interact preferentially with STIM1L compared to STIM1. STIM1L invalidation affected myoblast differentiation, with the formation of smaller myotubes, an effect similar to what we reported for TRPC1 and TRPC4 knockdown. On the contrary, the overexpression of STIM1L leads to the formation of larger myotubes. All together, these data strongly suggest that STIM1L and TRPC1/4 are working together in myotubes to ensure efficient store refilling and a proper differentiation program.
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: Inserm UMR S1180, Faculté de Pharmacie, Université Paris Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Sabourin
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.
authors.forename: Sophie
authors.initials: S
authors.lastname: Saüc
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.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Koenig
authors.affiliation: 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: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D002478:Cells, Cultured; D002675:Child, Preschool; D006801:Humans; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1 / Q000737:chemistry / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D020033:Protein Isoforms; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium
keywords: Calcium channel; SOCE; STIM1L; Skeletal muscle; TRPC