Graphical Abstract Highlights d Tensin positions integrins for Arf4-dependent endocytosis d Photoactivation-in-TIRF microscopy pinpoints the site for integrin endocytosis d Integrin endocytosis dictates recruitment of mTORC1 to nearby late endosomes d Proinvasive trafficking pathway is regulated by nutrient status SUMMARY Integrin trafficking is key to cell migration, but little is known about the spatiotemporal organization of integrin endocytosis. Here, we show that a5b1 integrin undergoes

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... sin-dependent centripetal movement from the cell periphery to populate adhesions located under the nucleus. From here, ligandengaged a5b1 integrins are internalized under control of the Arf subfamily GTPase, Arf4, and are trafficked to nearby late endosomes/lysosomes. Suppression of centripetal movement or Arf4-dependent endocytosis disrupts flow of ligand-bound integrins to late endosomes/lysosomes and their degradation within this compartment. Arf4-dependent integrin internalization is required for proper lysosome positioning and for recruitment and activation of mTOR at this cellular subcompartment. Furthermore, nutrient depletion promotes subnuclear accumulation and endocytosis of ligandengaged a5b1 integrins via inhibition of mTORC1. This two-way regulatory interaction between mTORC1 and integrin trafficking in combination with data describing a role for tensin in invasive cell migration indicate interesting links between nutrient signaling and metastasis.