Mechanisms of Clathrin-Independent Endocytosis

我们一直在研究网格蛋白独立形式的内吞作用（CIE），并已确定了一些内源性PM蛋白，通过这种机制进入细胞。 我们已经开始详细研究这些蛋白质，试图了解它们如何在细胞中旅行，以及它们是否与细胞机制特异性相互作用。 我们已经确定了CD44，CD98和CD147的细胞质尾部中的信号，这些信号负责改变它们的运输，并正在寻找负责识别和分选这些信号的细胞机制。 一些货物相互作用蛋白可以与细胞表面的货物结合。了解这些蛋白质如何进出细胞是很重要的，因为这些蛋白质参与与细胞外基质（CD44）的相互作用，参与营养转运（CD98），并与整合素和基质金属蛋白酶（CD147）相互作用。 为了促进这些研究，我们使用SNAP标签技术来量化特定细胞表面蛋白的内吞作用和再循环。 我们已经筛选了那些抑制或刺激CIE的FDA库化合物，并正在跟踪一种有希望的候选抑制剂。 我们也有兴趣研究CIE和网格蛋白介导的内吞作用（CME）之间的通信。

We have been studying clathrin-independent forms of endocytosis (CIE) and have identified a number of endogenous PM proteins that enter cells through this mechanism. We have begun to study these proteins in detail in an attempt to understand how they travel in cells and whether they specifically interact with cellular machinery. We have identified signals in the cytoplasmic tails of CD44, CD98 and CD147 that are responsible for their altered trafficking and are looking for cellular machinery that is responsible for recognition and sorting of these signals. Some of the cargo interacting proteins may associate with the cargo at the cell surface. Understanding how these proteins move into and out of cells is important because these proteins are involved in interaction with the extracellular matrix (CD44), are involved in nutrient transport (CD98) and interact with integrins and matrix metalloproteinases (CD147). To facilitate these studies we have used SNAP-tag technology to quantify endocytosis and recycling of specific cell surface proteins. We have screened FDA library compounds for those that inhibit or stimulate CIE and are following up on a promising candidate inhibitor. We have also been interested in examining the communication between CIE and clathrin-mediated endocytosis (CME).