Ligand-occupied integrin internalization links nutrient signaling to invasive migration

Rainero, E., Howe, J. D., Caswell, P. T., Jamieson, N. B. , Anderson, K., Critchley, D. R., Machesky, L. and Norman, J. C. (2015) Ligand-occupied integrin internalization links nutrient signaling to invasive migration. Cell Reports, 10(3), pp. 398-413. (doi: 10.1016/j.celrep.2014.12.037)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jamieson, Professor Nigel and Machesky, Professor Laura and Anderson, Professor Kurt and Norman, Professor James and Caswell, Dr Patrick and Rainero, Ms Elena
• Authors: Rainero, E., Howe, J. D., Caswell, P. T., Jamieson, N. B., Anderson, K., Critchley, D. R., Machesky, L., and Norman, J. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Reports
• Publisher: Elsevier Inc.
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Cell Repors 10(3):398-413
• Publisher Policy: Reproduced under a Creative Commons License