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Intracellular signals underlying the inductive effects of agrin during neuromuscular junction formation : study on the roles of ras and Shc

Agrin triggers the subsynaptic aggregation of acetylcholine receptor (AChR) via activation of the receptor tyrosine kinase MuSK (muscle-specific kinase). At present, the intracellular mechanisms utilized by MuSK to initiate such a complex process remain unknown. In the present study, I first tested if H-ras was involved in the process of synaptogenesis induced by agrin. The data presented suggest that ras could have a role in this process because a dominant inhibitory ras mutant (ras-N17) partially blocked the inductive effects of agrin while two activated ras mutants (ras-V12 and ras-V12-D38) induced agrin-independent AChR clusters. These effects were not due to major alterations in the levels of AChR, though more experiments are required to confirm these preliminary findings. / Second, I investigated whether the adaptor protein Shc was a downstream effector of activated MuSK. MuSK and Shc could be co-immunoprecipitated, but this association was not consistently observed nor was it modulated by agrin at all times. Generally, no alteration in Shc phosphotyrosine content was observed in response to agrin, and when an increase was detected, it was modest. Finally, agrin did not modulate the interaction between Shc and Grb2. Based on these results, I conclude that Shc interaction with MuSK is not regulated by agrin.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30684
Date January 2000
CreatorsLemaire, Mathieu.
ContributorsCarbonetto, Salvatore (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Biology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001746006, proquestno: MQ64388, Theses scanned by UMI/ProQuest.

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