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CYTOSKELETAL AND SIGNALING MECHANISMS REGULATING CILIARY TRAFFIC

调节纤毛交通的细胞骨架和信号传导机制

基本信息

批准号：
10237414
负责人：
PRACHEE AVASTHI
金额：
$ 41万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

项目摘要

Project Summary/Abstract A fundamental question in cell biology is how targeted intracellular protein trafficking is achieved and regulated. An excellent framework to ask this question is to study transport to a specific organelle or intracellular compartment. Trafficking of proteins to and into the eukaryotic flagellum is an ideal model to study polarized transport given that flagellar protein synthesis and trafficking can be induced experimentally on-demand, cargo proteins have been identified through proteomics and the ultimate cargo destination is localized to a very small region at the apical cell surface. This trafficking pathway was previously thought to only require microtubules and the regulation of microtubule motors through signaling pathways. Through quantitative analysis of flagellar motor dynamics in the canonical flagellar model system Chlamydomonas reinhardtii, we discovered that actin and an actin-based myosin motor play an important role in regulating the localization and compartmentalization of flagellar proteins. We also identified a variety of signaling pathways including a phosphatase, MKP-2, that are required for proper flagellar assembly. The broad goals of our work are to: 1) use chemical and genetic screening to identify novel pathways that integrate to control flagellar protein trafficking and molecular motors flagellar entry; and 2) use a toolbox of cellular and molecular assays to dissect the mechanisms by which they exert this control. We expect to uncover entirely new avenues for the study of secretory pathways conserved in all eukaryotes as well as novel functions for known genes in coordinated cellular trafficking.

项目总结/摘要细胞生物学中的一个基本问题是如何实现靶向的细胞内蛋白质运输，监管.提出这个问题的一个很好的框架是研究运输到特定的细胞器或细胞内车厢蛋白质在真核生物鞭毛中的运输是研究鞭毛极化的理想模型运输考虑到鞭毛蛋白质合成和运输可以通过实验按需诱导，货物蛋白质已经通过蛋白质组学鉴定，并且最终货物目的地定位于非常小的在顶端细胞表面的区域。这种运输途径以前被认为只需要微管以及通过信号通路调节微管马达。通过鞭毛的定量分析，马达动力学在典型的鞭毛模型系统衣原体reinhardtii，我们发现，肌动蛋白和肌动蛋白为基础的肌球蛋白马达在调节肌球蛋白的定位和区室化中起重要作用。鞭毛蛋白我们还鉴定了多种信号通路，包括磷酸酶MKP-2，这是鞭毛组装所必需的我们工作的主要目标是：1）使用化学和遗传筛选鉴定整合控制鞭毛蛋白运输和鞭毛分子马达的新途径进入; 2）使用细胞和分子测定工具箱来剖析它们发挥这种作用的机制控制我们希望能够为研究所有保守的分泌途径发现全新的途径。真核生物以及已知基因在协调细胞运输中的新功能。