Abstract 5122: Regulation of integrin trafficking by Rab proteins

Abstract

Abstract Integrins, the major receptors for cell adhesion to the extracellular matrix, are synthesized in the endoplasmic reticulum, transported in vesicles, and delivered to the plasma membrane or the cell surface by exocytosis. Like other receptors, integrins at the plasma membrane are constantly endocytosed, transported into endosomal compartments and then recycled back to the surface. Therefore, the density of integrins at the cell surface is ultimately determined by the balance between two vesicle trafficking events: endocytosis and exocytosis. Rab proteins are small (20-29 kDa) monomeric Ras-like GTPases that regulate vesicle budding, transport and tethering to the target membranes. Rab4, Rab11 and Rab25 function in the endocytic and recycling pathway. In this study, we examined roles of the Rab proteins in integrin trafficking. Silencing of Rab11 in HeLa cells had neither obvious effects on cell surface or total cellular expression of α3, α5 and β1 integrins nor on cell migration. Silencing of Rab25 reduced the surface expression of all three integrins and inhibited chemotactic migration. Surprisingly, Rab4 silencing dramatically increased both cell surface and total cellular expression of the integrins, and inhibited cell migration as well. These data suggest that Rab25 is required in integrin trafficking to the cell surface, and that Rab4 negatively regulates the expression and trafficking of integrins. These data support the notion that reduced or excessive integrins at the cell surface diminish cell motility. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5122.