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)

[img]
Preview
Text
102641.pdf - Published Version
Available under License Creative Commons Attribution.

7MB

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, Dr 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 > Institute 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

University Staff: Request a correction | Enlighten Editors: Update this record