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

突触特异性细胞外基质成分的结构和功能

• 批准号: 9310385
• 负责人: Arlene Chiu
• 金额: $ 24.92万
• 依托单位: Beckman Research Institute City of Hope
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-15 至 1997-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9310385&HistoricalAwards=false
• 关键词: Structure; Function; Synapse; Specific; Extracellular

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

小行星9310385 信息在神经细胞之间或神经细胞和肌肉细胞之间通过一种称为突触的特殊连接传递。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。 本项目将研究神经肌肉接头（神经和肌肉细胞之间的连接）中的这一过程。这种突触的形成似乎是由位于突触内的细胞外基质（ECM）内的稀有分子调节的。一种这样的分子可以是s-层粘连蛋白，一种最近描述的具有良好特征的分子层粘连蛋白的形式。 层粘连蛋白存在于肌细胞周围的ECM中，并促进神经元的轴突生长。相反，s-层粘连蛋白仅存在于神经肌肉接头处，并且似乎废除了层粘连蛋白的生长促进活性。 这提出了这样的可能性：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并启动突触形成的作用。 为了阐明s-层粘连蛋白的功能，需要大量纯化的分子，以及对其结构的理解。 然而，由于s-层粘连蛋白仅限于突触部位，因此这种分子在发育中的肌肉细胞周围存在非常少量。 最近，该实验室发现，在实验室中维持的癌细胞系产生并释放大量这种罕见分子。 此外，该细胞系还释放了第二种突触ECM分子，该分子可能与另一种普遍存在的ECM组分entactin相关。 该项目的目的是更好地表征s-层粘连蛋白和从细胞系中分离的新形式的巢蛋白。 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 SW 一个wwwwwwwkyw.com Y 小行星9310385 信息在神经细胞之间或神经细胞和肌肉细胞之间通过一种称为 ! ! F F F 8 Times New Roman 符号Arial“Univers（WN） D D D " H 男女比例 " B 8 Steve McLoon，IBN William普罗克特，IBN