囊泡运输和纤毛发育的缺陷因会导致多种疾病而成为研究热点。Exocyst 和 BBSome 都是高度保守的八聚体蛋白复合物。Exocyst 介导将囊泡拴系到靶膜上，并与纤毛发育有关。纤毛表面信号受体进出纤毛被BBSome及纤毛内转运机器所调控。小GTP酶BBS3在结合 GTP 后会驱动 BBSome 的装配从而帮助纤毛蛋白进入纤毛，然而 BBS3 如何激活仍然是个谜。我们发现 exocyst 的一个亚基 Sec8 可以与 BBS3 结合。因此我们推测 BBS3 与 exocyst 的结合对于调控原纤毛内蛋白运输起关键作用。我们将研究: 1). Exocyst 对 BBS3 激活和 BBSome 的胞内定位的影响。2). exocyst 和 BBSome 相互作用调控纤毛内蛋白运输的机制。这将有助于我们深入了解exocyst 和 BBSome 在纤毛发育和引发纤毛病中的分子机制。

Vesicle transport and ciliogenesis have become research focus since defects of them are implicated in many diseases. The exocyst and BBSome are both highly conserved octameric protein complexs. The exocyst functions to tethering vesicles to target membranes, and it also implicated in ciliogenesis. The sorting of signaling receptors into and out of cilia relies on the BBSome and the intraflagellar transport (IFT) machinery. GTP loading onto the small GTPase BBS3 drives assembly of a membrane-apposed BBSome coat that promotes cargo entry into cilia, yet how and where BBS3 is activated remains elusive. We identified an interaction between the exocyst subunit Sec8 and BBS3. We hypothesize that the interaction of BBS3 and the exocyst plays an essential role in the protein trafficking to the primary cilia. The exocyst-BBSome interaction coordinates vesicular transport and subsequent entry of proteins into cilia. In this study, we will: 1). Examine the effect of the exocyst on BBS3 activation and BBSome localization to the primary cilia. 2). Examine the role of the exocyst-BBSome interaction in the targeting of the ciliary proteins into the cilia. These studies will help us to understand the basic molecular mechanisms by which BBS3 and the exocyst contributes to primary ciliogenesis and ciliopathies.