title: Pannexin 1 and pannexin 3 channels regulate skeletal muscle myoblast proliferation and differentiation.
abstract: Pannexins constitute a family of three glycoproteins (Panx1, -2, and -3) forming single membrane channels. Recent work demonstrated that Panx1 is expressed in skeletal muscle and involved in the potentiation of contraction. However, Panxs functions in skeletal muscle cell differentiation, and proliferation had yet to be assessed. We show here that Panx1 and Panx3, but not Panx2, are present in human and rodent skeletal muscle, and their various species are differentially expressed in fetal versus adult human skeletal muscle tissue. Panx1 levels were very low in undifferentiated human primary skeletal muscle cells and myoblasts (HSMM) but increased drastically during differentiation and became the main Panx expressed in differentiated cells. Using HSMM, we found that Panx1 expression promotes this process, whereas it was impaired in the presence of probenecid or carbenoxolone. As for Panx3, its lower molecular weight species were prominent in adult skeletal muscle but very low in the fetal tissue and in undifferentiated skeletal muscle cells and myoblasts. Its overexpression (∼43-kDa species) induced HSMM differentiation and also inhibited their proliferation. On the other hand, a ∼70-kDa immunoreactive species of Panx3, likely glycosylated, sialylated, and phosphorylated, was highly expressed in proliferative myoblasts but strikingly down-regulated during their differentiation. Reduction of its endogenous expression using two Panx3 shRNAs significantly inhibited HSMM proliferation without triggering their differentiation. In summary, our results demonstrate that Panx1 and Panx3 are co-expressed in human skeletal muscle myoblasts and play a pivotal role in dictating the proliferation and differentiation status of these cells.
authors.affiliation: Department of Surgery, Division of Paediatric Surgery, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada,; Apoptosis Research Center, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Langlois
authors.affiliation: Apoptosis Research Center, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada,; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiang
authors.affiliation: Apoptosis Research Center, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Young
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia V5Z 4E8, Canada, and.
authors.forename: Bryce J
authors.initials: BJ
authors.lastname: Cowan
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Silvia
authors.initials: S
authors.lastname: Penuela
authors.affiliation: Department of Surgery, Division of Paediatric Surgery, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada,; Apoptosis Research Center, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada,; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada,. Electronic address: kcowan@cheo.on.ca.
authors.forename: Kyle N
authors.initials: KN
authors.lastname: Cowan
mesh_terms: D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D017630:Connexins / Q000378:metabolism / Q000502:physiology*; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology; D032448:Myoblasts, Skeletal / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010766:Phosphorylation; D011339:Probenecid / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D051381:Rats
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; C492765:PANX2 protein, human; C492766:PANX3 protein, human; D002229:Carbenoxolone; D011339:Probenecid
keywords: Differentiation; Myoblasts; Myogenesis; Pannexin; Proliferation; Skeletal Muscle