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Originally published In Press as doi:10.1074/jbc.M000571200 on July 14, 2000

J. Biol. Chem., Vol. 275, Issue 38, 29694-29700, September 22, 2000
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A Di-aromatic Motif in the Cytosolic Tail of the Mannose Receptor Mediates Endosomal Sorting*

Anja SchweizerDagger , Philip D. Stahl§, and Jack RohrerDagger ||

From the Dagger  Friedrich Miescher Institut, Maulbeerstrasse 66, 4058 Basel, Switzerland and the § Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

The mannose receptor (MR), the prototype of a new family of multilectin receptor proteins important in innate immunity, undergoes rapid internalization and recycling from the endosomal system back to the cell surface. Sorting of the MR in endosomes prevents the receptor from entering lysosomes where it would be degraded. Here, we focused on a diaromatic sequence (Tyr18-Phe19) in the MR cytoplasmic tail as an endosomal sorting signal. The subcellular distribution of chimeric constructs between the MR and the cation-dependent mannose 6-phosphate receptor was assessed by Percoll density gradients and cell surface assays. Unlike the wild type constructs, mutant receptors with alanine substitutions of Tyr18-Phe19 were highly missorted to lysosomes, indicating that the di-aromatic motif of the MR cytoplasmic tail mediates sorting in endosomes. Within this sequence Tyr18 is the key residue with Phe19 contributing to this function. Moreover, Tyr18 was also found to be essential for internalization, consistent with the presence of overlapping signals for internalization and endosomal sorting in the cytosolic tail of the MR.

A di-aromatic amino acid sequence in the cytosolic tail has now been shown to function in two receptors known to be internalized from the plasma membrane, the MR and the cation-dependent mannose 6-phosphate receptor. This feature therefore appears to be a general determinant for endosomal sorting.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by National Institutes of Health Grant 2R01AI20015-16.

|| Supported by a Prof. Max Cloëtta fellowship. To whom correspondence should be addressed. Tel.: 41 61 697 7609; Fax: 41 61 697 3976; E-mail: Rohrer@fmi.ch.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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