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 differ entiation of retinal pigmented epithelia and the epidermis. It encodes a ty pe I transmembrane glycoprotein that shares significant sequence homologies with several melanosomal proteins. We have studied its intracellular traff ic in both pigmented and non-pigmented cells. We report that a di-leucine-b ased sorting signal (ExxPLL) present in the cytoplasmic domain of QNR-71 is necessary and sufficient for its proper targeting to the endosomal/premela nosomal compartments of both pigmented and non-pigmented cells. The intrace llular transport of QNR-71 to these compartments is mediated by the AP-3 as sembly proteins. As previously observed for the lysosomal glycoproteins Lam pI and LimpII, overexpression of QNR-71 increases the amount of AP-3 associ ated with membranes, and inhibition of AP-3 synthesis increases the routing of QNR-71 towards the cell surface. In addition, expression of QNR-71 indu ces a misrouting of endogenous LampI to the cell surface. Thus, the targeti ng of QNR-71 might be similar to that of the lysosomal integral membrane gl ycoproteins LampI and LimpII. This suggests that sorting to melanosomes and lysosomes requires similar sorting signals and transport machineries.