An unconventional dileucine-based motif and a novel cytosolic motif are required for the lysosomal and melanosomal targeting of OA1.

Journal of Cell Science
Rosanna PiccirilloM V Schiaffino

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

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Citations

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
Apr 17, 2012·Physiology·Anand Sitaram, Michael S Marks
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
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Feb 4, 2014·Current Biology : CB·Tiziana DanieleMaria Vittoria Schiaffino
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Jul 12, 2016·Expert Opinion on Therapeutic Targets·Yuyang HuangYongchang Yao
Oct 11, 2016·The Journal of Investigative Dermatology·Elisabetta De FilippoPrashiela Manga
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Jul 17, 2009·Genetic Testing and Molecular Biomarkers·Lucia MicaleGiuseppe Merla
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May 27, 2016·The Journal of Biological Chemistry·Lian GelisHanns Hatt
Aug 8, 2021·International Journal of Molecular Sciences·Beatriz BueschbellAnke C Schiedel

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