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