REGULATION OF APICAL ENDOCYTOSIS BY ARF6 AND PLD

上皮细胞形成膜片，作为组织隔室之间的界面。特定大分子通过这一屏障的运输对大多数组织的正常运作至关重要。上皮细胞的质膜分为两个亚域，以完成特异性和定向运输；顶端面向外部环境或组织腔，基底外侧面向其他上皮细胞和细胞外基质。这些结构域维持着不同的蛋白质组成，并且每个结构域的运输都受到独特的调节。囊泡运输的调节是由Ras超家族的小GTPases进行的，包括adp -核糖基化因子（ARFs）。一种ARF蛋白ARF6在非极化细胞的内吞途径中起作用，似乎可能调节极化上皮细胞的顶极内吞作用。本研究的总体目标是确定ARF6及其潜在的下游效应物磷脂酶D在极化上皮细胞顶极内吞作用中的作用。

Epithelial cells form membrane sheets which serve as a interface between tissue compartments. The transport of specific macromolecules across this barrier is critical to the proper functioning of most tissues. In order to accomplish specific and directional transport, the plasma membrane of epithelial cells is divided into two subdomains; apical facing the exterior environment or the tissue lumen, and basolateral facing other epithelial cells and the extracellular matrix. These domains maintain distinct protein compositions, and trafficking at each of these domains is uniquely regulated. Regulation of vesicle transport is carried out by small GTPases of the Ras superfamily, including ADP-ribosylation factors (ARFs). One ARF protein, ARF6, functions in the endocytic pathway in non-polarized cells and seems likely to regulate endocytosis at the apical pole of polarized epithelial cells. The overall aim of this proposal is to define the role of ARF6 and a potential downstream effector, phospholipase D, in endocytosis at the apical pole of polarized epithelial cells.