EXTRACELLULAR MATRIX NERVE TERMINAL ANCHORAGE PROTEIN

在神经再生过程中，细胞外基质(ECM)引导 神经肌肉接头的重建。的活动区 突触前质膜的神经递质释放似乎是 根据突触细胞外基质的提示进行重建。据推测，跨膜 神经末梢ECM受体(神经末梢锚定蛋白)结合 这些突触的ECM信号并形成了与胞浆、胞吐的联系 神经末梢的机械。我们发现了一条潜在的神经 末端ECM受体，一个由4种蛋白质和一个跨膜组成的蛋白质复合体 蛋白多糖，SV2pg。我们称这种蛋白质复合体为SV2pg复合体。 SV2pg复合体是突触囊泡膜的组成部分，具有 细胞外基质受体所具有的特性。1)除了成为 在突触小泡中，这个复合体位于神经末梢。 突触前质膜的表面。2)亚细胞分馏 电子器官的研究表明，尽管大多数SV2pg是在突触中 囊泡，有相当数量的小泡与细胞外基质紧密结合。3)我们发现 纯化的SV2pg复合体与电子器官ECM的一个组分结合 萃取物。4)SV2pg复合体与层粘连蛋白结合。层粘连蛋白是一种已知的 突触细胞外基质的成分，在电子器官细胞外基质中含量丰富 萃取物。 我们建议检验SV2pg复合体作为ECM的假设 神经末梢表面受体：L)我们将全面描述 SV2pg复合体，并确定如何将组件从一个 又一个。2)我们将确定SV2pg是否变得紧密关联 在神经肌肉交界处的突触发生过程中有突触细胞外基质。3) 我们将确定是否可以在以下期间阻止此关联 用SV2pg复合体的抗体观察突触发生 这种阻塞对由此产生的突触结构的影响。4)我们会 尝试分离SV2pg复合体的ECM配体并确定 该络合物的哪一组分与配体结合。如上所述，这 配体可能是层粘连蛋白。 通过成功完成我们的研究，我们希望能获得一些 对构建突触的分子事件的理解 在突触发生过程中。此外，由于SV2pg复合体是突触 囊泡成分，可能是一种细胞外基质受体，我们可以解释 突触的活性依赖性黏附机制。

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.