MOLECULAR BIOLOGY OF NEURAL FUNCTION

下面的摘要描述了三个项目， 驱动蛋白轻链（KLC）、nsec-1和酸性钙调蛋白（AC）在 神经功能 第四章考察了信号的下游目标 在神经肌肉接头处诱导的转导酶 来自海兔的肌调节蛋白和颊蛋白肽家族 加利福尼亚州。 KLC和nsec-1是影响突触囊泡的蛋白质 (SV)运输 我们已经鉴定了至少九种KLC亚型， 鱿鱼的视叶，目前正在集中精力确定功能 C端尾部结构域的 我们也在探讨这个问题， 使用同源重组技术通过基因敲除分析 重组我们以前已经确定nsec-1作为一种调节剂， 神经元Cdk5激酶活性。几 关于nsec-1的突变如何影响SV运输的问题仍然存在。 我们目前正在努力确定剩余的组成部分， nsec-1/Cdk5复合物，并确定它们各自的功能，因为它们 与Cdk5活性有关。 AC是碱性磷酸酶的非平滑肌亚型， 我们已经显示的钙调蛋白定位于发育中的生长锥， 神经元 AC水平随着神经元的分化而降低， 在独特的C-末端尾部结构域中的调节结构域，包括PEST 结构域、异戊二烯化位点、P环元件和酪氨酸 磷酸化位点都表明调节蛋白质第二 信使诱导的易位和蛋白质周转。 目前的研究 旨在解决这些结构域如何与蛋白质 功能 我们还参与了鉴定twitchin，一种750 kDa的 肌肉蛋白，作为ARC后PK-A磷酸化的主要靶点 用神经肽肌调节蛋白进行肌肉刺激治疗动脉瘤 加利福尼亚州。 进一步的工作是针对阐明受体和 信号转导级联反应的其他下游靶点 神经肽buccalin和myomodulin的刺激

The following summary describes three projects examining the roles of kinesin light chains (KLC), nsec-1 and acidic calponin (AC) play in neural function. The fourth examines the downstream targets of signal transduction enzymes induced at the neuromuscular junction by the myomodulin and buccalin peptide families from the sea hare Aplysia californica. KLCs and nsec-1 are proteins that effect synaptic vesicle (SV) transport. We have identified at least nine isoforms of KLC from squid optic lobe and are currently focussing on determining the function of the C-terminal tail domains. We are also pursuing this question in vivo by genetic knockout analysis using the technique of homologous recombination. We have previously identified nsec-1 as a regulator of neuronal Cdk5 kinase activity towards neurofilament proteins. Several questions remain regarding how mutation of nsec-1 affects SV trafficking. We are currently endeavoring to identify the remaining components of the nsec-1/Cdk5 complex and determine their respective functions as they relate to Cdk5 activity. AC is a nonsmooth muscle isoform of basic calponin that we have shown localizes to the developing growth cones of neurons. AC levels diminish as neurons differentiate and a number of regulatory domains in the unique C-terminal tail domain including a PEST domain, an isoprenylation site, a P-loop element and a tyrosine phosphorylation site all suggest mechanisms for regulating protein second messenger-induced translocation and protein turnover. Current research is directed toward addressing how these domains relate to protein function. We have also participated in identifying twitchin, a 750 kDa muscle protein, as a primary target of PK-A phosphorylation following ARC muscle stimulation with the neuro peptide myomodulin in Aplysia californica. Further work is directed towards elucidating receptors and other downstream targets of the signal transduction cascades in response to stimulation by the neuropeptides buccalin and myomodulin.