近年来研究发现G蛋白在分泌和内吞途径的细胞器上行使一些非传统（non-canonical）功能。我们的合作者发现Gαs蛋白参与调控EGFR和GPCR从早期内体分选进入溶酶体降解，我们最近发现Gαs是泛素结合蛋白，含有与内体分选蛋白复合体中类似的泛素结合结构域，并且激活Gαs可增强泛素的结合。泛素结合结构域为Gαs参与调控EGFR早期内体分选所必需，但其中的分子机制尚需深入的研究。本研究以Gαs的泛素结合能力为对象，探明Gαs是否通过泛素结合结构域参与内体分选蛋白复合体的组装来调控早期内体分选，以及Gαs的活性是否影响早期内体分选，并探讨这一机制对细胞学功能的潜在影响。本项目首次研究Gαs作为泛素结合蛋白参与早期内体分选的机制，研究成果有助于我们深入理解Gαs介导的细胞学功能，也可为今后以Gαs为靶点治疗相关疾病提供新的理论基础。

Research over the past decade has established that G proteins have non-canonical roles acting along both the endocytic and secretory pathways. Several studies have confirmed that Gαs participate in the endosomal sorting of EGFR and several GPCRs.We recently found that Gαs is a ubiquitin-binding protein. The ubiquitin interaction motif (similar as those from ESCRT proteins) identified at the N-terminus of Gαs is essential for Gαs to control EGFR endosomal sorting. However, the mechanism of action of the ubiquitin interaction motif of Gαs in this sorting step needs to be characterized. This project is aim to clarify whether Gαs integrates with ESCRT machinery through ubiquitin interaction motif to facilitate endosomal sorting. We will then check the effect of Gαs activity on this sorting strategy, which will finally help us to explore the consequence impact on physiological function. It is the first try to unveil the mechanism of Gαs in endosomal sorting through its ubiquitin binding capacity. The expected results will promote the understanding the cellular functions mediated by Gαs, and hence give hints on developing treatment for diseases through targeting Gαs.