Role of ColQ, a specific collagen in the functionn.. (ColQ and the NMJ)
Role of ColQ, a specific collagen in the functionnal organisation of the neuromuscular junction
(ColQ and the NMJ)
Start date: 01 Jan 2008,
End date: 31 Dec 2009
My research project is based on one principal axis: how extracellular matrix proteins participate to the functional organisation of the synapse. The goal of my research project is to study ColQ induced regulation of acetylcholine receptor (AChR) expression process. Recently, during a collaborative project between Jean Cartaud and Claire Legay groups, we have shown that the C-terminal part of ColQ interacts with MuSK (muscle-specific tyrosine kinase receptor) ectodomain. This association is not only responsible for anchoring AChE in the synaptic basal lamina but could also play an important role in regulating AChR expression. Other works have shown that ColQ interacts with another partner, the perlecan, an extracellular matrix heparan sulfate proteoglycan (HSPG) interacting with the Dystroglycan (DG). Based on these evidence, we hypothesized that ColQ could regulate the number of AChR via MuSK and/or perlecan/dystroglycan pathways. These signalling pathways would then be used as pivot adapting the number of AChE molecules to the number of AChR. Preliminary results from the laboratory confirm this hypothesis and suggest that ColQ regulates AChR and synaptic proteins expression and also suggest that ColQ may act via the two signalling pathways MuSK and perlecan/dystroglycan. Using various complementary approaches of biochemistry, cellular and molecular biology both in vitro and in vivo in mice, I will identify the signalling pathways induced by ColQ, in particular those involving ColQ/perlecan/dystroglycan and ColQ/MuSK. This study will allow me to better understand the mechanisms by which ColQ controls the postsynaptic domain differentiation at the NMJ.
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