REGULATION OF APICAL ENDOCYTOSIS BY ARF6 AND PLD

上皮细胞形成膜片，作为组织间的界面。特定的大分子通过这一屏障的运输对大多数组织的正常功能至关重要。为了完成特定和定向的转运，上皮细胞的质膜被分为两个亚区：顶端面向外部环境或组织管腔，基端面向其他上皮细胞和细胞外基质。这些结构域保持着不同的蛋白质组成，每个结构域的运输都受到独特的调控。囊泡运输的调节是由RAS超家族的小GTP酶完成的，包括ADP核糖化因子(ARF)。ARF蛋白ARF6在非极化细胞的内吞途径中发挥作用，似乎可能调节极化上皮细胞顶端的内吞作用。这项建议的总体目标是确定ARF6和一个潜在的下游效应因子，磷脂酶D，在极化上皮细胞顶端的内吞作用中的作用。

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.