PI(3,4)P <sub>2</sub> -mediated membrane tubulation promotes integrin trafficking and invasive cell migration
Zhen Feng, Cheng‐han Yu
Abstract
Significance The dynamic distribution of phosphoinositide lipids orchestrates intracellular compartmentalization and protein sorting. Here, we report the PI(3,4)P 2 -dependent endocytosis of adhesion receptor integrin-beta3 at the invadopodium and its implication in promoting invasive cell migration. PI(3,4)P 2 -rich compartment in the plasma membrane contains integrin-beta3 and is actively internalized through SNX9-mediated membrane invagination as well as dynein-mediated membrane tubulation along cortical microtubule tracks. Accelerated integrin endocytosis promotes adhesion turnover, and subsequent integrin exocytosis further supports cell migration. In general, the functional link between PI(3,4)P 2 biogenesis and membrane internalization can be applicable to other membrane molecules at the invadopodium and provide insights into the regulation of cell migration.