Abstract
The protein product of the gene responsible for ocular albinism type 1, named OA1, is a pigment-cell-specific membrane glycoprotein, displaying features of G-protein-coupled receptors, yet exclusively localized to late endosomes, lysosomes and melanosomes. To dissect the signals responsible for the intracellular localization of OA1, we generated chimeric proteins consisting of the cytosolic domains of OA1 fused to the lumenal and transmembrane domains of LAMP1; in addition, we generated missense and deletion mutants of full-length OA1. Using this approach, we identified two separate sorting signals that are both necessary and sufficient for intracellular retention, as well as lysosomal and melanosomal localization, in melanocytic and non-melanocytic cells. These sorting signals are an unconventional dileucine motif within the third cytosolic loop and a novel motif, characterized by a tryptophan-glutamic acid doublet, within the C-terminal tail. Both motifs must be mutated to promote the plasma membrane localization of OA1, suggesting that they can independently drive its intracellular targeting. In addition, both motifs act similarly as lysosomal sorting signals in non-melanocytic cells, but appear to carry different specificit...Continue Reading
References
Nov 1, 1976·Archives of Ophthalmology·F E O'DonnellD L Stone
Sep 1, 1990·The Journal of Cell Biology·M A Williams, M Fukuda
Dec 1, 1983·The Journal of Cell Biology·D K MillerR A Firestone
May 1, 1980·Histopathology·A Garner, B S Jay
Jul 1, 1995·The Journal of Investigative Dermatology·S J Orlow
Nov 1, 1993·Journal of Virology·C A Deminie, M Emerman
Feb 1, 1996·The Journal of Cell Biology·J RohrerS Kornfeld
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·M V SchiaffinoA Ballabio
Apr 23, 1999·The Journal of Biological Chemistry·P A CalvoM S Marks
Sep 2, 1999·Nature Genetics·M V SchiaffinoA Ballabio
Jul 6, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E C Dell'AngelicaJ S Bonifacino
Jul 8, 2000·Pigment Cell Research·V Setaluri
Dec 15, 2000·Human Molecular Genetics·M d'AddioM V Schiaffino
Jan 21, 2001·The Journal of Biological Chemistry·S CherquiC Antignac
Feb 22, 2001·Experimental Eye Research·P SamaraweeraS J Orlow
Feb 24, 2001·Human Genetics·M T BassiM V Schiaffino
Mar 22, 2001·Traffic·B ShenS J Orlow
Mar 27, 2001·The Journal of Cell Biology·G RaposoM S Marks
Aug 30, 2001·Proceedings of the National Academy of Sciences of the United States of America·T KushimotoV J Hearing
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·M S Marks, M C Seabra
Jan 5, 2002·Pigment Cell Research·B Shen, S J Orlow
May 29, 2002·Human Gene Therapy·Maria Vittoria SchiaffinoMichele De Luca
Mar 20, 2003·Journal of Proteome Research·Venkatesha BasrurEttore Appella
Mar 26, 2003·Annual Review of Biochemistry·Juan S Bonifacino, Linton M Traub
Jul 25, 2003·Trends in Biochemical Sciences·Adriano MarcheseJeffrey L Benovic
Mar 16, 1963·Nature·M SEIJIM S BIRBECK
Dec 31, 2003·Molecular Biology of the Cell·Aija KyttäläJ Paul Luzio
Oct 8, 2004·The Journal of Biological Chemistry·Stephan StorchThomas Braulke
Jul 21, 2005·Pigment Cell Research·M Vittoria Schiaffino, Carlo Tacchetti
Citations
Jun 15, 2011·Nature Cell Biology·Claudia G AlmeidaEvelyne Coudrier
Mar 9, 2011·Médecine sciences : M/S·Cédric DelevoyeGraça Raposo
Jul 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ilaria PalmisanoMaria Vittoria Schiaffino
Sep 8, 2010·The Journal of Biological Chemistry·Tobias Stauber, Thomas J Jentsch
Jan 1, 2009·Molecular Biology of the Cell·Anand SitaramMichael S Marks
Aug 14, 2008·Human Molecular Genetics·Ilaria PalmisanoMaria Vittoria Schiaffino
Sep 1, 2009·Human Molecular Genetics·Francesca GiordanoGraça Raposo
Apr 17, 2012·Physiology·Anand Sitaram, Michael S Marks
Sep 23, 2010·Physiological Genomics·Young Ah Seo, Shannon L Kelleher
Sep 6, 2013·Journal of Cell Science·Thomas BurgoyneClare E Futter
Oct 3, 2008·PLoS Biology·Vanessa M LopezBrian S McKay
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Francesca GiordanoGraça Raposo
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ping YuJia Qu
Oct 9, 2007·Experimental Eye Research·Michio Sone, Seth J Orlow
Apr 22, 2010·Traffic·Pieter SteenhuisStephan Storch
Apr 28, 2012·Traffic·Nataliya Y KomarovaDoris Rentsch
Apr 10, 2010·Traffic·Ozlem DemirelRupert Abele
Jan 30, 2015·The Biochemical Journal·Katalin KissGergely Szakacs
Feb 4, 2014·Current Biology : CB·Tiziana DanieleMaria Vittoria Schiaffino
Dec 3, 2008·Biochimica Et Biophysica Acta·Thomas Braulke, Juan S Bonifacino
Jul 12, 2016·Expert Opinion on Therapeutic Targets·Yuyang HuangYongchang Yao
Oct 11, 2016·The Journal of Investigative Dermatology·Elisabetta De FilippoPrashiela Manga
Dec 31, 2016·International Journal of Molecular Sciences·Catherine StaudtMarielle Boonen
Jul 17, 2009·Genetic Testing and Molecular Biomarkers·Lucia MicaleGiuseppe Merla
Mar 4, 2014·The Journal of Biological Chemistry·Morié IshidaMitsunori Fukuda
Oct 22, 2019·Frontiers in Pharmacology·Yoshio GoshimaAderemi Caleb Aladeokin
Sep 24, 2020·Molecular Biology of the Cell·Linh LeMichael S Marks
May 27, 2016·The Journal of Biological Chemistry·Lian GelisHanns Hatt
Jun 24, 2020·Neuron·Lief E FennoKarl Deisseroth
Aug 8, 2021·International Journal of Molecular Sciences·Beatriz BueschbellAnke C Schiedel