MOLECULAR MECHANISMS OF THE ELP COMPLEX AND ASSOCIATED FACTORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的实验室长期以来一直有兴趣了解Rab蛋白在膜交通中激活的分子事件，我们最近通过遗传筛选分离了IKAP的酵母同系物Elp 1 p，以确定调节Rab GTdR作用的因素。FD综合征蛋白质与其他五种蛋白质形成复合物，称为延长复合物。我们的研究揭示了Elp复合物在调节极化胞吐作用中的重要细胞质作用[1]。人类ELP 1基因的突变是神经系统疾病家族性自主神经功能障碍的原因之一。本研究的长期目标是阐明FD病证蛋白的作用机制以及IKAP失调导致临床症状的途径。 这里提出的项目旨在了解Elp 1 p和Elongator复合物调节极化分泌和生长的分子机制。为了鉴定在Elp途径中起作用的其他基因和蛋白质，我们进行了额外的遗传筛选，从而鉴定出一种蛋白质，该蛋白质是通过翻译后修饰改变生长控制蛋白的潜在靶标。结合Elp 3 p的乙酰化活性鉴定靶点和修饰实体将有助于我们理解调节极化分泌和细胞生长的分子机制。

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. Our lab has had a long-standing interest in understanding the molecular events underlying the activation of Rab proteins in membrane traffic, and we recently isolated the yeast homolog of IKAP, Elp1p, via a genetic screen to identify factors regulating Rab GTPase action. The FD syndrome protein is found in a complex with five other proteins, termed the Elongator complex. Our studies revealed an essential cytoplasmic role for the Elp complex in the regulation of polarized exocytosis [1]. Mutations in the human ELP1 gene are a cause of the neurological disorder Familial Dysautonomia. The long-term goal of the research is to elucidate the mechanism of the FD disease syndrome protein and the pathway leading from IKAP dysregulation to the clinical symptoms. The project proposed here is directed at understanding the molecular mechanisms by which Elp1p and the Elongator complex regulate polarized secretion and growth. To identify other genes and proteins that act in the Elp pathway we have conducted additional genetic screens that have resulted in the identification of a protein that is a potential target for altering growth control proteins via post-translational modification. Identification of the targets and modified entities in conjunction with the acetylation activities of Elp3p will help us understand the molecular mechanisms that regulate polarized secretion and cell growth.