Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin-integrin complexes

Developmental Cell
Viola Hélène LobertHarald Stenmark

Abstract

Cell migration requires endocytosis and recycling of integrins, but it is not known whether degradation of these membrane proteins is involved. Here we demonstrate that in migrating cells, a fraction of the endocytosed fibronectin receptor, alpha 5 beta 1 integrin, is sorted into multivesicular endosomes together with fibronectin and degraded in lysosomes. This sorting requires fibronectin-induced ubiquitination of the alpha 5 subunit, and the activity of the endosomal sorting complex required for transport (ESCRT) machinery, which interacts with alpha 5 beta 1 integrin. Importantly, we demonstrate that both alpha 5 ubiquitination and ESCRT functions are required for proper migration of fibroblasts. We propose that ligand-mediated degradation of alpha 5 beta 1 integrin via the ESCRT pathway is required in order to prevent endosomal accumulation of ligand-bound integrins that might otherwise form nonproductive adhesion sites. Fibronectin and alpha 5 beta 1 integrin therefore are trafficked to lysosomes in a similar way to growth factors and their receptors.

References

Mar 1, 1990·Journal of Cellular Physiology·M M Sczekan, R L Juliano
Oct 1, 1987·The Journal of Cell Biology·J E Murphy-Ullrich, D F Mosher
Mar 1, 1994·The Journal of Cell Biology·T E O'TooleM H Ginsberg
Jun 20, 1995·Proceedings of the National Academy of Sciences of the United States of America·Z ZhangE Ruoslahti
Jul 1, 1993·The Journal of Cell Biology·J S BauerR L Juliano
May 26, 1995·The Journal of Biological Chemistry·P E HughesM H Ginsberg
Feb 1, 1995·Matrix Biology : Journal of the International Society for Matrix Biology·S GodynaW S Argraves
Mar 22, 1996·The Journal of Biological Chemistry·P E HughesM H Ginsberg
Oct 1, 1996·The International Journal of Biochemistry & Cell Biology·E Marchina, S Barlati
Nov 18, 1998·Current Opinion in Cell Biology·S D Shapiro
Mar 24, 1999·The Journal of Cell Biology·C D Nobes, A Hall
May 4, 2002·Nature Cell Biology·Camilla RaiborgHarald Stenmark
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·David J KatzmannScott D Emr
Mar 18, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Denise C Hocking, Cecilia H Chang
Nov 18, 2003·Histochemistry and Cell Biology·David J GilloolyHarald Stenmark
Dec 6, 2003·Science·Anne J RidleyAlan Rick Horwitz
Apr 9, 2004·Nature Reviews. Molecular Cell Biology·Jean Gruenberg, Harald Stenmark
Nov 26, 2004·Molecular Biology of the Cell·Jane Sottile, Jennifer Chandler
Sep 9, 2005·The EMBO Journal·Kaisa Haglund, Ivan Dikic
Feb 1, 2006·Traffic·Patrick T Caswell, Jim C Norman
Feb 25, 2006·Nature Reviews. Cancer·Sam M Janes, Fiona M Watt
May 13, 2006·Annual Review of Biophysics and Biomolecular Structure·James H Hurley, Scott D Emr
May 19, 2006·Molecular Biology of the Cell·M Razi, C E Futter
Jun 7, 2006·The Journal of Cell Biology·Teijo PellinenJohanna Ivaska
Jun 8, 2006·The Journal of Biological Chemistry·Dipankar RayHiroaki Kiyokawa
Sep 9, 2006·Journal of Cell Science·Teijo Pellinen, Johanna Ivaska
Aug 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuichi SekineTadashi Matsuda
Mar 12, 2008·Biochemical and Biophysical Research Communications·Teresa M BrophyNiamh Moran
Sep 23, 2008·Developmental Cell·Teijo PellinenJohanna Ivaska

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Citations

Dec 24, 2011·Nature Cell Biology·Tor Erik RustenHarald Stenmark
May 9, 2012·Nature Cell Biology·Ralph Thomas BöttcherReinhard Fässler
Aug 19, 2010·Nature Reviews. Molecular Cell Biology·Iley Ozerlat
Jun 29, 2011·The Journal of Biological Chemistry·Songyu WangDavis T W Ng
Sep 2, 2011·The Journal of Biological Chemistry·Ajit TiwariAmit Choudhury
Dec 14, 2011·Molecular Biology of the Cell·Nina RintanenVarpu Marjomäki
Jul 27, 2012·Molecular Biology of the Cell·Barbara SchroederMark A McNiven
Jan 25, 2013·Molecular Biology of the Cell·Moorthy KrishnanJames R Goldenring
Jan 6, 2011·Science·Christine Métin, Camilla Luccardini
Nov 29, 2011·International Journal of Cell Biology·Sejeong ShinSang-Oh Yoon
Dec 4, 2012·Molecular Cancer Research : MCR·Lynn M KnowlesJan Pilch
Dec 14, 2011·Journal of Cell Science·Feng Shi, Jane Sottile
Oct 3, 2012·Journal of Cell Science·Rebecca E BridgewaterPatrick T Caswell
May 29, 2013·Pharmacology & Therapeutics·Yasuhito OnoderaHisataka Sabe
Jul 27, 2014·The Journal of Surgical Research·Henry C HsiaSiobhan A Corbett
Jun 15, 2011·Annual Review of Cell and Developmental Biology·Johanna Ivaska, Jyrki Heino
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Daniela Silva-AyalaCarlos F Arias
Aug 22, 2014·Human Molecular Genetics·Andreia Neves-CarvalhoPatrícia Maciel
Jul 27, 2012·Annual Review of Cell and Developmental Biology·Phyllis I Hanson, Anil Cashikar
Mar 20, 2014·Molecular Membrane Biology·Claudia Mattissek, David Teis
Dec 26, 2015·Biology·Mirka HomrichSimone Diestel
Nov 2, 2011·The Journal of Cell Biology·Matteo Bonazzi, Pascale Cossart
Apr 12, 2012·The Journal of Cell Biology·Florian SteinbergPeter J Cullen
Dec 8, 2015·Nature Cell Biology·Massiullah Shafaq-ZadahLudger Johannes
Oct 6, 2015·Nature Cell Biology·Jonna AlankoJohanna Ivaska
Jul 25, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kay O SchinkHarald Stenmark
Apr 27, 2011·Traffic·Catherine Sem WegnerHarald Stenmark
Nov 20, 2015·Current Biology : CB·Nikki R PaulPatrick T Caswell
Apr 5, 2016·Nature Cell Biology·Guilherme P F NaderGregg G Gundersen
Jan 28, 2012·The Biochemical Journal·Antje SchaeferPeter L Hordijk
Jan 27, 2015·Biochemical Society Transactions·Katarzyna I Wolanska, Mark R Morgan
May 15, 2015·Nature Communications·Bong Hwan SungAlissa M Weaver
Oct 16, 2010·Cell Adhesion & Migration·Micha Nethe, Peter L Hordijk
Apr 3, 2014·Small GTPases·Pablo MendozaVicente A Torres
Oct 19, 2012·Cell Adhesion & Migration·Tobias ZechLaura M Machesky
Feb 19, 2011·Communicative & Integrative Biology·Viola Hélène Lobert, Harald Stenmark

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