The Structure and Function of Synapse-Specific, Extracellular Matrix Components

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9310385 Chiu Information is relayed between nerve cells or a nerve cell and a muscle cell by a specialized connection called a synapse. The formation of synapses occurs during development, but little is currently known about the mechanisms responsible for this developmental process. This project will study this process in the neuromuscular junction, the connection between nerve and muscle cells. The formation of this synapse appears to be regulated by rare molecules located within the extracellular matrix (ECM) within the synapse. One such molecule may be s-laminin, a recently described form of the well characterized molecule, laminin. Laminin is present in the ECM surrounding the muscle cells and promotes axon growth from neurons. In contrast, s-laminin is only present at the neuromuscular junction and appears to abrogate the growth-promoting activity of laminin. This raises the possibility that during development, laminin promotes and guides neurons toward potential target cells, while s-laminin may act to terminate growth and initiate synapse formation. To elucidate the function of s-laminin requires large quantities of purified molecule, as well as an understanding of its structure. However, because s-laminin is restricted to synaptic sites, this molecule is present in very small amounts around developing muscle cells. Recently, this laboratory found that a cancer cell line, maintained in the laboratory, produced and released large amount of this rare molecule. In addition, this cell line also released a second synaptic ECM molecule that may be related to another ubiquitous ECM component, entactin. The aim of this project is to better characterize s-laminin and the novel form of entactin isolated from the cell line. Most importantly, the role of these molecules in the formation and function of the neuromuscular junction will be studied. *** Q =Q l sw A wwwwwww KÕ Y 9310385 Chiu Information is relayed between nerve cells or a nerve cell and a muscle cell by a specialized connection called ! ! F f f 8 Times New Roman Symbol & Arial " Univers (WN) d d d " h L %M E " b 8 Steve McLoon, IBN William Proctor, IBN