Ligand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive Migration.

Elena Rainero, Jonathan D Howe, Patrick T Caswell, Nigel B Jamieson, Kurt Anderson, David R Critchley, Laura Machesky, Jim C Norman

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Integrin trafficking is key to cell migration, but little is known about the spatiotemporal organization of integrin endocytosis. Here, we show that α5β1 integrin undergoes tensin-dependent centripetal movement from the cell periphery to populate adhesions located under the nucleus. From here, ligand-engaged α5β1 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 ligand-engaged α5β1 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.
    Original languageEnglish
    JournalCell Reports
    DOIs
    Publication statusPublished - 15 Jan 2015

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