NSF Award
9022382
The mature nervous system functions, in part, because precise connections are made and maintained between appropriate groups of nerve cells. The formation of these specialized sites of connectivity, known as synapses, occurs during development, however only a small amount of information is known about the mechanisms that influence this critical process. This investigation will focus on the neuromuscular junction, a model synapse between motor nerve cells and muscle cells. The formation of the neuromuscular synapse appears to be regulated by specialized molecules within the extracellular matrix. Laminin, a well characterized matrix molecule, is present in all extracellular matrices and is a potent promoter of neurite outgrowth. In contrast, S-laminin, known as synaptic laminin, is a homolog of laminin which is localized within the neuromuscular synaptic cleft and appears to exhibit selective adhesiveness for motor neurons. Instead of promoting growth, S-laminin acts to terminate axonal growth and initiate synapse formation. The long term goal of this research project is to understand the molecular mechanisms that contribute to the formation and maintenance of neuromuscular synapses. The immediate goal is to determine the function, structure, and association of S-laminin with other components in the synaptic extracellular matrix. Experiments, utilizing a Schwannoma cell line, will be performed to purify and biochemically characterize this molecule. This specific cell line produces and releases large amounts of this rare antigen in the form of a soluble complex with other matrix compounds. Results from this study will facilitate future studies on the role of this synaptic molecule in the formation of the neuromuscular junction.
