Muscle specific kinase in synaptic adaptation
This project will investigate the role of postsynaptic Muscle specific Kinase (MuSK) in regulating presynaptic neurotransmitter release at the neuromuscular junction.
MuSK is a receptor tyrosine kinase in the postsynaptic membrane of the neuromuscular junction (NMJ). Gene knockout studies in mice show that a signalling pathway involving neural agrin, LRP4, MuSK, DOK7 and rapsyn is essential for stabilizing postsynaptic membrane specializations at the developing NMJ. It remains unclear how the MuSK signalling pathway influences presynaptic nerve terminal specialization and adaptation to synaptic challenges. This project will test the effect of forced expression of components of the MuSK signalling pathway, and of inhibiting MuSK signalling, upon presynaptic transmitter release and synaptic adaptation. Intracellular electrophysiology and confocal fluorescence microscopy will be used to assess structural and functional adaptations of the NMJ under conditions where MuSK signalling is either enhanced or suppressed.
Effective adaptation of the nerve terminal to the challenge of synaptic failure is likely to be critical to maintaining nerve-muscle connections in motor neuron disease and in conditions like sedentary aging. This project will discover the role of the MuSK system in this vital adaptive response of the nerve terminal.
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The opportunity ID for this research opportunity is: 16
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