EXTRACELLULAR MATRIX NERVE TERMINAL ANCHORAGE PROTEIN

在神经再生过程中，细胞外基质（ECM）指导神经再生。 神经肌肉接头的重建。活动区域， 突触前质膜的神经递质释放似乎是 根据突触ECM的线索重建。据推测，跨膜 神经末梢ECM受体（神经末梢锚定蛋白）结合 这些突触ECM线索，并形成一个链接到胞质，胞吐 神经末梢的机器我们发现了一条潜在的神经 末端ECM受体，4种蛋白和跨膜蛋白的蛋白复合物， 蛋白多糖，SV2pg。我们称这种蛋白质复合物为SV2pg复合物。 SV2pg复合物是突触囊泡膜的组分， ECM受体的预期特性。1)除了作为一部分 在突触囊泡中，这种复合体存在于神经末梢 在突触前质膜表面。2)亚细胞分离 说明虽然SV2pg大部分位于突触内， 囊泡中，显著量与ECM紧密结合。3)我们发现 纯化的SV2pg复合物与电器官ECM的组分结合 萃取物4)SV2pg复合物与层粘连蛋白结合。层粘连蛋白是已知的 突触ECM的成分，并在电器官ECM中丰富 萃取物 我们建议测试SV2pg复合物作为ECM的假设， 神经末梢表面上的受体：l）我们将充分表征 SV2pg复合物，并确定如何从一个 另2)我们将确定SV2pg是否与 在神经肌肉接头处的突触发生过程中与突触ECM发生作用。第三章 我们将决定是否可以在 用SV2pg复合物的抗体进行突触发生， 这种阻塞对所产生的突触结构的影响。4)我们将 尝试分离SV2pg复合物的ECM配体并确定 复合物的哪一种组分结合配体。如上所述，这 配体可以是层粘连蛋白。 通过成功完成我们的研究，我们希望能获得一些 了解突触形成过程中的分子活动 在突触形成过程中。此外，由于SV2pg复合物是突触 囊泡成分和可能的ECM受体，我们可以阐明一个 突触的活性依赖性粘附机制。

During nerve regeneration, extracellular matrix (ECM) directs the rebuilding of the neuromuscular junction. Active zones for neurotransmitter release in the presynaptic plasma membrane appear to be rebuilt following cues of the synaptic ECM. Presumably, transmembrane nerve terminal ECM receptors (nerve terminal anchorage proteins) bind these synaptic ECM cues and form a link to the cytosolic, exocytotic machinery of the nerve terminal. We have identified a potential nerve terminal ECM receptor, a protein complex of 4 proteins and a transmembrane proteoglycan, SV2pg. We call this protein complex the SV2pg complex. The SV2pg complex is a component of the synaptic vesicle membrane and has the properties expected of an ECM receptor. 1) In addition to being part of the synaptic vesicle, this complex is found on the nerve terminal surface in the presynaptic plasma membrane. 2) Subcellular fractionation of electric organ demonstrates that, although most SV2pg is in synaptic vesicles, a significant amount is tightly bound to ECM. 3) We find that the purified SV2pg complex binds to a component of the electric organ ECM extracts. 4) The SV2pg complex binds to laminin. Laminin is a known component of the synaptic ECM and is abundant in electric organ ECM extracts. We propose to test the hypothesis that the SV2pg complex acts as an ECM receptor on the nerve terminal surface: l) We will fully characterize the SV2pg complex and determine how to isolate the components from one another. 2) We will determine whether the SV2pg becomes tightly associated with synaptic ECM during synaptogenesis at the neuromuscular junction. 3) We will determine whether we can block this association during synaptogenesis with antibodies to the SV2pg complex and look at the effects of this blockage on the resulting synaptic structure. 4) We will attempt to isolate the ECM ligand for the SV2pg complex and determine which component of the complex binds the ligand. As mentioned above, this ligand may be laminin. From successful completion of our research we hope to gain some understanding of the molecular events involved in building the synapse during synaptogenesis. In addition, since the SV2pg complex is a synaptic vesicle component and perhaps an ECM receptor, we may elucidate an activity-dependent adhesion mechanism of the synapse.