Mechanisms of Clathrin-Independent Endocytosis

我们一直在研究不依赖网格蛋白的内吞作用（CIE）形式，并已经确定了一些内源性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，试图了解它们是如何在细胞中移动的，以及它们是否与细胞机制特异性地相互作用。我们已经在CD44、CD98和CD147的细胞质尾部识别出了导致其转运改变的信号，并正在寻找负责识别和分类这些信号的细胞机制。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，参与营养物质运输（CD98），并与整合素和基质金属蛋白酶（CD147）相互作用。

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. 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 are using SNAP-tag technology to quantify endocytosis and recycling of specific cell surface proteins. We are currently looking for compounds that inhibit or stimulate CIE. We have also been interested in examining the communication between CIE and clathrin-mediated endocytosis (CME). In examining the effects of Pitstop, a newly discovered inhibitor of CME, we found that it was also a potent inhibitor of CIE. Pitstop had been identified through a biochemical assay and although it does inhibit CME, it has broader effects.