Integrins Regulate Rac Targeting by Internalization of Membrane Domains

TLDR

Integrin-mediated adhesion is required for Rac1 translocation to the plasma membrane, and integrin signals may regulate lipid raft localization to control domain‑specific signaling in anchorage‑dependent cells. Active Rac1 preferentially associates with low‑density, cholesterol‑rich membranes, and integrin‑mediated internalization of cholesterol and raft markers during cell detachment disrupts this targeting; blocking internalization preserves Rac1 membrane localization and effector activation even in nonadherent cells.

Abstract

Translocation of the small GTP-binding protein Rac1 to the cell plasma membrane is essential for activating downstream effectors and requires integrin-mediated adhesion of cells to extracellular matrix. We report that active Rac1 binds preferentially to low-density, cholesterol-rich membranes, and specificity is determined at least in part by membrane lipids. Cell detachment triggered internalization of plasma membrane cholesterol and lipid raft markers. Preventing internalization maintained Rac1 membrane targeting and effector activation in nonadherent cells. Regulation of lipid rafts by integrin signals may regulate the location of membrane domains such as lipid rafts and thereby control domain-specific signaling events in anchorage-dependent cells.