The AP-3-dependent targeting of the melanosomal glycoprotein QNR-71 requires a di-leucine-based sorting signal.
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.
Le Borgne
R
R
Institut de Biologie de Lille, CNRS EP525, Institut Pasteur de Lille, France.
Planque
N
N
Martin
P
P
Dewitte
F
F
Saule
S
S
Hoflack
B
B
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
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