The role of ubiquitylation in receptor endocytosis and endosomal sorting

Journal of Cell Science
Kaisa Haglund, Ivan Dikic

Abstract

Ligand-induced activation of transmembrane receptors activates intracellular signaling cascades that control vital cellular processes, such as cell proliferation, differentiation, migration and survival. Receptor signaling is modulated by several mechanisms to ensure that the correct biological outcome is achieved. One such mechanism, which negatively regulates receptor signaling, involves the modification of receptors with ubiquitin. This post-translational modification can promote receptor endocytosis and targets receptors for lysosomal degradation, thereby ensuring termination of receptor signaling. In this Commentary, we review the roles of ubiquitylation in receptor endocytosis and degradative endosomal sorting by drawing on the epidermal growth factor receptor (EGFR) as a well-studied example. Furthermore, we elaborate on the molecular basis of ubiquitin recognition along the endocytic pathway through compartment-specific ubiquitin-binding proteins and highlight how endocytic sorting machineries control these processes. In addition, we discuss the importance of ubiquitin-dependent receptor endocytosis for the maintenance of cellular homeostasis and in the prevention of diseases such as cancer.

References

Aug 4, 1995·Biochemical and Biophysical Research Communications·S MoriY Saito
May 30, 1997·The Journal of Biological Chemistry·S van DelftP M van Bergen en Henegouwen
Oct 6, 1997·The EMBO Journal·J M Galan, R Haguenauer-Tsapis
Nov 14, 1997·Trends in Biochemical Sciences·A Varshavsky
Apr 18, 1998·The Journal of Cell Biology·A BenmerahN Cerf-Bensussan
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·S MiyakeH Band
Aug 11, 1998·Nature·J M GaullierR Aasland
Oct 6, 1998·Annual Review of Biochemistry·A Hershko, A Ciechanover
Nov 1, 2000·Cell·J Schlessinger
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Apr 3, 2001·Nature Reviews. Molecular Cell Biology·C B Thien, W Y Langdon
Sep 5, 2001·The EMBO Journal·C RaiborgH Stenmark
Apr 16, 2002·Molecular Biology of the Cell·Martin SachseJudith Klumperman
May 4, 2002·Nature Cell Biology·Camilla RaiborgHarald Stenmark
May 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Andy WongArnold Li
May 15, 2002·The EMBO Journal·Owen PornillosWesley I Sundquist
Jun 11, 2002·Nature Cell Biology·Patricia S BilodeauRobert C Piper
Jun 20, 2002·The Journal of Biological Chemistry·Elsa KlapiszPaul M P van Bergen en Henegouwen
Jul 18, 2002·Current Biology : CB·Carla E OldhamJohn P O'Bryan
Aug 15, 2002·The Journal of Biological Chemistry·Iwona SzymkiewiczIvan Dikic
Sep 5, 2002·Biochemical and Biophysical Research Communications·Alexander Shekhtman, David Cowburn
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kaisa HaglundIvan Dikic
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·David J KatzmannScott D Emr
Jan 29, 2003·The Journal of Biological Chemistry·Kristi G BacheHarald Stenmark
Mar 13, 2003·Molecular Biology of the Cell·Xuejun JiangAlexander Sorkin

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Citations

Aug 31, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Agnieszka Swiatecka-Urban
Jan 23, 2013·Molecular Neurobiology·Laura CampelloJosé Martín-Nieto
Apr 24, 2013·Nature Reviews. Molecular Cell Biology·Carmine SettembreAndrea Ballabio
Nov 7, 2012·The Journal of Biological Chemistry·Bart-Jan de KreukPeter L Hordijk
May 2, 2013·PLoS Pathogens·Katja MöllekenJohannes H Hegemann
Nov 26, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Robert Roskoski
Jul 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·FoSheng HsuYuxin Mao
Oct 22, 2013·Oncogene·B Nadratowska-WesolowskaA Wiedlocha
Nov 26, 2013·FEBS Letters·Yue ZhouHiroaki Sakurai
Dec 26, 2015·Biology·Mirka HomrichSimone Diestel
Aug 8, 2014·Membranes·Vibeke Bertelsen, Espen Stang
May 10, 2012·FEBS Letters·Simin Rahighi, Ivan Dikic
Sep 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kamila KalinowskaErika Isono
Aug 6, 2014·Journal of Proteome Research·Vyacheslav AkimovBlagoy Blagoev
Feb 13, 2016·Biomolecules & Therapeutics·Min-Young LeeKyung-Chul Choi
Aug 3, 2013·Traffic·Jason S SilvermanJames D Bangs
Jul 28, 2015·Cell Reports·Richa Madan LomashKatherine W Roche
Dec 17, 2014·Development, Growth & Differentiation·Yue XiongYun Zhao
Oct 3, 2014·Molecular Plant Pathology·Bo LiLibo Shan
Jun 19, 2015·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Tadashi Nakagawa, Keiko Nakayama
May 28, 2015·European Journal of Endocrinology·Marily TheodoropoulouMasayuki Komada
Aug 21, 2013·Biochimie·Tânia FranciscoCláudia P Grou
Apr 9, 2013·Biochimica Et Biophysica Acta·Nina Bergbold, Marius K Lemberg
May 27, 2015·Biochemical Society Transactions·Teresa M Ribeiro-RodriguesHenrique Girao

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