The role of heparansulfate proteoglycan agrin at the retina - basal lamina interface in the developing CNS

Agrin是一种广泛表达于大多数器官的硫酸肝素蛋白多糖。然而，Agrin的功能在神经肌肉连接处得到了最好的理解，在那里它负责大多数（如果不是全部的话）突触后特化的形成、维持和再生，包括含有乙酰胆碱受体、乙酰胆碱酯酶和其他分子的聚集体。Agrin还调节神经肌肉连接处突触特异性基因的表达。选择性剪接产生几种不同分布和生物活性的农业蛋白异构体。所有的agrin亚型都在发育中的中枢神经系统中通过神经元和神经胶质细胞表达，但agrin在中枢神经系统中的功能尚不清楚。本应用程序的主要目的是分析agrin在特定中枢神经系统基底层（视网膜内限制膜）中的作用，确定体内参与agrin与基底层相互作用的agrin结构域，确定邻近视网膜细胞中agrin的结合伙伴，并研究与基底层结合的agrin对直接对抗的胶质细胞膜中分子分布的可能影响。这些研究有望使我们更好地了解基底膜相关蛋白在中枢神经系统发育过程中的作用，以及细胞外基质在中枢神经系统中的作用。

Agrin is a heparansulfate proteoglycan which is widely expressed throughout most organs. Agrin´s function, however, is best understood at the neuromuscular junction where it is responsible for the formation, maintenance and regeneration of most if not all postsynaptic specializations, including aggregates containing acetylcholine receptors, acetylcholine esterase and other molecules. Agrin also regulates synapse-specific gene expression at the neuromuscular junction. Alternative splicing generates several agrin isoforms which differ in their distribution and biological activity. All agrin isoforms are expressed throughout the developing CNS by neurons and glial cells, but the function of agrin in the CNS is unknown. The main goal of this application is to analyze the role of agrin in a particular CNS basal lamina, the retinal inner limiting membrane, to identify the domains of agrin involved in the interaction of agrin with a basal lamina in vivo, to identify binding partners of agrin in the adjacent retinal cells, and to investigate a possible influence of basal lamina-bound agrin on the distribution of molecules in the directly-apposed glial cell membrane. These studies will hopefully lead to a better understanding of the role of basal lamina-associated agrin during CNS-development and of the role of the extracellular matrix in the CNS in general.