The goal of this proposal is to understand the role of a synapse-specific carbohydrate, N-acetylgalactosamine (Ga1NAc), in the formation of the neuromuscular synapse. The expression of this carbohydrate during the development of the rodent neuromuscular synapse will be studied and its role in the formation of this synapse will be assessed by performing experiments on rodent muscle cells in culture. The preliminary data suggest that: 1) Ga1NAc serves as a molecular signal for the synaptic expression of muscle proteins and 2) Ga1NAc-containing molecules in muscle participate in the synaptic signaling mechanism. These two hypotheses will be tested in this proposal, using the following three specific aims:
In Aim 1, the development of the neuromuscular junction will be studied.
In Aim 2, it will be determined if Ga1NAc is necessary for the synaptic localization of extracellular matrix or membrane proteins in cultured muscle.
In Aim 3, Ga1NAc-containing molecules that participate in the synaptic signaling mechanism in cultured muscle will be identified. The identification of a role for Ga1NAc in the targeting of synaptic proteins or in synaptic signaling at the neuromuscular junction would provide new therapeutic avenues for the treatment of neuromuscular diseases.
|Martin, P T; Scott, L J; Porter, B E et al. (1999) Distinct structures and functions of related pre- and postsynaptic carbohydrates at the mammalian neuromuscular junction. Mol Cell Neurosci 13:105-18|