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

9310385丘脑信息通过一种称为突触的特殊连接在神经细胞或神经细胞和肌肉细胞之间传递。突触的形成发生在发育过程中，但目前对这一发育过程的机制知之甚少。这个项目将研究神经肌肉连接的这一过程，即神经和肌肉细胞之间的连接。这种突触的形成似乎受到位于突触内的细胞外基质(ECM)内的稀有分子的调控。一个这样的分子可能是S-层粘连蛋白，这是最近描述的一种具有良好特征的分子，层粘连蛋白。层粘连蛋白存在于肌肉细胞周围的细胞外基质中，并促进神经元的轴突生长。相反，S-层粘连蛋白只存在于神经肌肉接头处，似乎可以消除层粘连蛋白促进生长的活性。这增加了这样一种可能性，即在发育过程中，层粘连蛋白促进并引导神经元走向潜在的靶细胞，而S-层粘连蛋白可能起到终止生长和启动突触形成的作用。要阐明S-层粘连蛋白的功能，需要大量纯化的分子，以及对其结构的了解。然而，由于S-层粘连蛋白仅限于突触部位，这种分子存在于发育中的肌肉细胞周围，数量非常少。最近，该实验室发现，实验室维持的一种癌细胞株产生并释放了大量这种稀有分子。此外，该细胞系还释放了第二个突触ECM分子，可能与另一种普遍存在的ECM成分entactin有关。本项目的目的是为了更好地表征S-层粘连蛋白和从细胞系中分离出的新型粘连蛋白。最重要的是，这些分子在神经肌肉接头的形成和功能中的作用将被研究。*Q=Q L通过一种特殊的连接在神经细胞或神经细胞和肌肉细胞之间传递信息，这种连接称为！！F f f 8 Times New Roman符号&amp；Arial“Uns(WN)d d”h L%M E“b 8 Steve McLoon，IBN William Proctor，IBN

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