Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size
type: Dataset
contact point: Organization
  fn: CCSD
keyword: infoeu-reposemanticsdoctoralthesis
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: differenciation-myogenique
keyword: myogenic-differenciation
keyword: biochimie
keyword: biochemistry
keyword: phospholipase-d
keyword: biosciences
keyword: theses
landing page: https://theses.hal.science/tel-00679827
description: Phospholipase D (PLD) hydrolyzes phosphatidylcholine of cell membranes, releasing the lipid messenger phosphatidic acid. The ability of PLD to affect mTOR signaling pathway, a central actor in the control of muscle tissue, prompted us to study its role in this tissue. My thesis aims at investigating how PLD is involved in myogenic differentiation, and how it regulates muscle mass. We first showed that the mechanism by which PLD controls differentiation of L6 myoblasts involves the activation of the two mTOR complexes (mTORC1 and mTORC2). mTORC2 activates differentiation, probably via its effector PKCalpha, whereas mTORC1 represses differentiation via its effector S6K1, by inducing the phosphorylation of Rictor, a component of mTORC2, and the inhibition of this complex. Besides, we showed that extinction of PLD by RNA interference induces the atrophy of L6 myotubes, and decreases the phosphorylation of the mTORC1 effectors S6K1 and 4E-BP1. Conversely, overexpression of PLD using adenoviral vectors induces the hypertrophy of myotubes and the activation of both mTORC1 pathway and the mTORC2 effector Akt. Furthermore, PLD overexpression attenuates atrophy induced by dexamethasone. These results highlight a hypertrophic and anti-atrophic role of PLD, which could be achieved through stimulation of the mTOR pathway. Our results suggest that PLD is likely to play a key role in skeletal muscle homeostasis, by acting at both the tissue regeneration and mass regulation levels.
identifier: NNT: 2011ISAL0009
issued: 2026-05-24T10:41:18.814668
language: fr
modified: 2026-05-24T10:41:18.814673

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Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size
type: Distribution
access URL: https://theses.hal.science/tel-00679827
format: HTML
issued: 2026-05-24T10:41:18.882538
modified: 2026-05-24T10:41:18.791179