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Journal of Cell Science 114, 2831-2841 (2001)
© 2001 The Company of Biologists Limited


RESEARCH ARTICLE

The AP-3-dependent targeting of the melanosomal glycoprotein QNR-71 requires a di-leucine-based sorting signal

Roland Le Borgne*, Nathalie Planque{ddagger}, Patrick Martin{ddagger}, Frédérique Dewitte, Simon Saule{ddagger} and Bernard Hoflack§

Institut de Biologie de Lille, CNRS EP525, Institut Pasteur de Lille, BP 447, 59021 Lille cedex, France
* Present address: Ecole Normale Supérieure, CNRS équipe ATIPE/UMR 8544, 46, rue d'Ulm, 75230 Paris cedex 05, France
{ddagger} Present address: UMR 146, Institut Curie- Section de recherche, Centre Universitaire, Bâtiment 110, 91405 Orsay Cedex, France
§ Present address: UMR 144, Institut Curie, 26, rue d'Ulm, 75248 Paris cedex 5, France
Author for correspondence (e-mail: bernard.hoflack{at}curie.fr )

Accepted May 1, 2001

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 LampI 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.

Key words: AP-3, Retina, Glycoproteins, Sorting, Melanosome


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