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|Title:||Ligand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive Migration.|
Howe, J. D.
Caswell, P. T.
Jamieson, N. B.
Critchley, David R.
Norman, J. C.
|Publisher:||Elsevier (Cell Press)|
|Citation:||Cell Reports, 2015 10, 398–413|
|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.|
|Rights:||This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).|
|Appears in Collections:||Published Articles, Dept. of Cell Physiology and Pharmacology|
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