REGULATION OF APICAL ENDOCYTOSIS BY ARF6 AND PLD

ARF6 和 PLD 对顶端内吞作用的调节

• 批准号: 2861398
• 负责人: Lorraine C Santy
• 金额: $ 1.36万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2861398
• 关键词: MDCK cell; antibody receptor; apical membrane; biological signal transduction; bombesin; endocytosis; enzyme activity; epidermal growth factor; gene mutation; growth factor; guanine nucleotide binding protein; phospholipase D; protein transport

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.

上皮细胞形成膜片，作为组织室之间的界面。 特定的大分子在该障碍物上的运输对于大多数组织的正确功能至关重要。 为了完成特定和方向的转运，将上皮细胞的质膜分为两个亚域。面向外部环境或组织腔的顶端，以及面向其他上皮细胞和细胞外基质的基底外侧。 这些结构域保持独特的蛋白质组成，并且在这些领域中的每个域中进行运输受到唯一的调节。 囊泡转运的调节是由RAS超家族的小GTP酶进行的，包括ADP-核糖基化因子（ARFS）。 一种ARF蛋白ARF6在非偏振细胞的内吞途径中起作用，并且似乎可能调节极化上皮细胞的顶端内吞作用。 该提案的总体目的是定义ARF6的作用和潜在的下游效应子磷脂酶D在极化上皮细胞的顶端内吞作用中。