title: Phospholipase D regulates myogenic differentiation through the activation of both mTORC1 and mTORC2 complexes.
abstract: How phospholipase D (PLD) is involved in myogenesis remains unclear. At the onset of myogenic differentiation of L6 cells induced by the PLD agonist vasopressin in the absence of serum, mTORC1 complex was rapidly activated, as reflected by phosphorylation of S6 kinase1 (S6K1). Both the long (p85) and short (p70) S6K1 isoforms were phosphorylated in a PLD1-dependent way. Short rapamycin treatment specifically inhibiting mTORC1 suppressed p70 but not p85 phosphorylation, suggesting that p85 might be directly activated by phosphatidic acid. Vasopressin stimulation also induced phosphorylation of Akt on Ser-473 through PLD1-dependent activation of mTORC2 complex. In this model of myogenesis, mTORC2 had a positive role mostly unrelated to Akt activation, whereas mTORC1 had a negative role, associated with S6K1-induced Rictor phosphorylation. The PLD requirement for differentiation can thus be attributed to its ability to trigger via mTORC2 activation the phosphorylation of an effector that could be PKCα. Moreover, PLD is involved in a counter-regulation loop expected to limit the response. This study thus brings new insights in the intricate way PLD and mTOR cooperate to control myogenesis.
authors.affiliation: Lyon University, France.
authors.forename: Rami
authors.initials: R
authors.lastname: Jaafar
authors.forename: Caroline
authors.initials: C
authors.lastname: Zeiller
authors.forename: Luciano
authors.initials: L
authors.lastname: Pirola
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Grazia
authors.forename: Fabio
authors.initials: F
authors.lastname: Naro
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Etienne
authors.initials: E
authors.lastname: Lefai
authors.forename: Georges
authors.initials: G
authors.lastname: Némoz
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D024510:Muscle Development / Q000187:drug effects; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D001127:Arginine Vasopressin; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D010739:Phospholipase D