Motoneurone - Jonction Neuromusculaire et Membrane Musculaire
Wednesday, March 27, 2019
Parallel-1
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27-AM-Parallel-1
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11:00 AM
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12:30 PM
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Motoneurone - Jonction Neuromusculaire et Membrane Musculaire
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Amphi A
11:00 AM
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S10-01
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Regulation of neuromuscular connectivity by Wnt signaling: from signaling molecule to therapeutic strategies
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L.
Laure
STROCHLIC
11:30 AM
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S10-02
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An in vivo model for the functional validation of polymorphisms in genes required for AChR synthesis
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J-L.
Jean-Louis
BESSEREAU
12:00 PM
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S10-03
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Sarcolemmal membrane repair activated by conserved intracellular signaling responses can compensate for membrane fragility in muscular dystrophy
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N.
Noah
WEISLEDER
Objectives : A conserved plasma membrane repair mechanism exists to counteract sarcolemmal membrane damage in muscle cells, restore membrane barrier function, and maintain muscle cell homeostasis. Membrane damage induced by various insults requires an effective repair mechanism and any disruption of the process gives rise to several pathophysiological states. Previous studies indicate that compromised repair capacity in striated muscle can lead to muscular dystrophy and that increasing membrane repair capacity can have therapeutic effects in animal models of muscular dystrophy. This membrane repair response can involve various cellular mechanisms to repair large disruptions in the sarcolemmal membrane, including activation of signaling pathways that trigger vesicular trafficking to the site of injury followed by vesicular fusion with the damaged portion of the membrane to patch the membrane disruption. Multiple proteins, including dysferlin, TRIM72/MG53, and various annexins, participate in this repair response. Numerous studies have shown that several aspects of vesicle trafficking are dependent on the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathway. In this study, membrane repair assays on skeletal muscle and non-muscle cell lines demonstrated that the membrane repair process is dependent on activation of the PI3K signaling axis through the downstream target Akt1. This signaling response facilitates the function of TRIM72/MG53 in membrane repair since blocking PI3K or Akt1 minimizes the elevated membrane repair produced by TRIM72/MG53 overexpression. One mechanism found to increase membrane repair following TRIM72/MG53 overexpression or PI3K/Akt1 activation is elevated exocytotic and endocytotic activity. Further, multi-photon microscopy studies indicate that the PI3K/Akt1 pathway is relevant to membrane repair in isolated mouse muscle bundles injured because PI3K or Akt1 inhibition prevents membrane resealing. Dystrophic skeletal muscle and cardiac tis
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