Structure and Function of S-Laminin, A Synaptic Form of Laminin

成熟的神经系统的功能部分是因为在适当的神经细胞群之间建立和维持了精确的连接。这些被称为突触的专门连接部位的形成发生在发育过程中，然而，关于影响这一关键过程的机制，人们只知道少量的信息。这项研究将集中在神经肌肉接头，运动神经细胞和肌肉细胞之间的模型突触。神经肌肉突触的形成似乎是由细胞外基质内的专门分子调节的。层粘连蛋白是一种特征性的基质分子，存在于所有细胞外基质中，是神经突生长的有效促进剂。相比之下，S-层粘连蛋白，称为突触层粘连蛋白，是层粘连蛋白的同系物，其位于神经肌肉突触间隙内，并且似乎表现出对运动神经元的选择性抑制。S-层粘连蛋白不是促进生长，而是终止轴突生长并启动突触形成。本研究项目的长期目标是了解有助于神经肌肉突触形成和维持的分子机制。当前的目标是确定S-层粘连蛋白的功能、结构以及与突触细胞外基质中其他成分的关联。实验，利用神经鞘瘤细胞系，将进行纯化和生物化学表征这种分子。这种特异性细胞系以与其他基质化合物的可溶性复合物的形式产生并释放大量的这种罕见抗原。这项研究的结果将有助于进一步研究这种突触分子在神经肌肉接头形成中的作用。

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.