ACTIN-BINDING PROTEINS IN A POSTSYNAPTIC PREPARATION: LASP-1 IS A COMPONENT OF

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。中枢神经系统突触是细胞间通讯的复杂位点。突触蛋白质组分的鉴定和表征将有助于更好地理解神经传递和可塑性的机制。我们应用多维蛋白鉴定技术（MudPIT）对纯化的、胍溶解的突触后组分进行鉴定，以鉴定新的突触定位分子。我们确定了几个肌动蛋白相关蛋白，已知可调节肌动蛋白聚合和控制非神经细胞的细胞运动，这些蛋白以前未与中枢神经系统突触功能相关。其中之一是lap -1，一种与肌动蛋白相关的含有LIM和SH3结构域的蛋白。我们发现lasp-1在中枢神经系统神经元中强烈表达，并集中在突触部位。总的来说，肌动蛋白相关蛋白在突触后密度部分的优势，特别是那些参与肌动蛋白重组的蛋白，表明有许多模式可以影响突触f -肌动蛋白聚合状态，从而影响突触生理。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CNS synapses are complex sites of cell-cell communication. Identification and characterization of the protein components of synapses will lead to a better understanding of the mechanisms of neurotransmission and plasticity. We applied multidimensional protein identification technology (MudPIT) to purified, guanidine-solubilized postsynaptic fractions to identify novel synaptically localized molecules. We identified several actin-associated proteins known to regulate actin polymerization and control cell motility in nonneural cells that have not previously been associated with CNS synaptic function. One of these is lasp-1, an actin-associated LIM and SH3 domain-containing protein. We show that lasp-1 is strongly expressed by CNS neurons and is concentrated at synaptic sites. Overall, the preponderance of actin-associated proteins in postsynaptic density fractions, and specifically those involved in actin reorganization, suggests that there are many modes by which the state of synaptic F-actin polymerization and, hence, synaptic physiology are affected.