Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/36027
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dc.contributor.authorRainero, E.-
dc.contributor.authorHowe, J. D.-
dc.contributor.authorCaswell, P. T.-
dc.contributor.authorJamieson, N. B.-
dc.contributor.authorAnderson, K.-
dc.contributor.authorCritchley, David R.-
dc.contributor.authorMachesky, L.-
dc.contributor.authorNorman, J. C.-
dc.date.accessioned2015-12-08T15:47:26Z-
dc.date.available2015-12-08T15:47:26Z-
dc.date.issued2015-01-15-
dc.identifier.citationCell Reports, 2015 10, 398–413en
dc.identifier.issn2211-1247-
dc.identifier.urihttp://www.sciencedirect.com/science/article/pii/S2211124714010663en
dc.identifier.urihttp://hdl.handle.net/2381/36027-
dc.description.abstractIntegrin 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.en
dc.language.isoenen
dc.publisherElsevier (Cell Press)en
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/25600874-
dc.rightsThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).en
dc.titleLigand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive Migration.en
dc.typeJournal Articleen
dc.identifier.doi10.1016/j.celrep.2014.12.037-
dc.identifier.eissn2211-1247-
dc.identifier.piiS2211-1247(14)01066-3-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJOURNAL ARTICLE-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departmentsen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Molecular & Cell Biologyen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Canceren
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/RESULTen
dc.dateaccepted2014-12-16-
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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