title: The AP-3-dependent targeting of the melanosomal glycoprotein QNR-71 requires a di-leucine-based sorting signal.
abstract: The Quail Neuroretina clone 71 gene (QNR-71) is expressed during the differentiation of retinal pigmented epithelia and the epidermis. It encodes a type I transmembrane glycoprotein that shares significant sequence homologies with several melanosomal proteins. We have studied its intracellular traffic in both pigmented and non-pigmented cells. We report that a di-leucine-based sorting signal (ExxPLL) present in the cytoplasmic domain of QNR-71 is necessary and sufficient for its proper targeting to the endosomal/premelanosomal compartments of both pigmented and non-pigmented cells. The intracellular transport of QNR-71 to these compartments is mediated by the AP-3 assembly proteins. As previously observed for the lysosomal glycoproteins Lampl and LimpII, overexpression of QNR-71 increases the amount of AP-3 associated with membranes, and inhibition of AP-3 synthesis increases the routing of QNR-71 towards the cell surface. In addition, expression of QNR-71 induces a misrouting of endogenous LampI to the cell surface. Thus, the targeting of QNR-71 might be similar to that of the lysosomal integral membrane glycoproteins LampI and LimpII. This suggests that sorting to melanosomes and lysosomes requires similar sorting signals and transport machineries.
authors.affiliation: Institut de Biologie de Lille, CNRS EP525, Institut Pasteur de Lille, France.
authors.forename: R
authors.initials: R
authors.lastname: Le Borgne
authors.forename: N
authors.initials: N
authors.lastname: Planque
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Dewitte
authors.forename: S
authors.initials: S
authors.lastname: Saule
authors.forename: B
authors.initials: B
authors.lastname: Hoflack
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D034041:Monomeric Clathrin Assembly Proteins; D016296:Mutagenesis / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000502:physiology*; D021382:Protein Sorting Signals / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D011784:Quail; D014162:Transfection
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D021382:Protein Sorting Signals; C100584:QNR-71 protein, Coturnix japonica; C439023:clathrin assembly protein AP180; D007930:Leucine