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Originally published In Press as doi:10.1074/jbc.M410752200 on December 14, 2004
J. Biol. Chem., Vol. 280, Issue 8, 7309-7316, February 25, 2005
Recognition of the Tryptophan-based Endocytosis Signal in the Neonatal Fc Receptor by the µ Subunit of Adaptor Protein-2*
Naomi L. B. Wernick ,
Volker Haucke , and
Neil E. Simister ¶
From the
Rosenstiel Center for Basic Biomedical Sciences and Department of Biology, Brandeis University, Waltham, Massachusetts 02254-9110 and the Free University Berlin, Institute of Chemistry-Biochemistry, Takustrasse 6, Berlin 14195, Germany
Endocytosis of membrane proteins is typically mediated by signals present in their cytoplasmic domains. These signals usually contain an essential tyrosine or pair of leucine residues. Both tyrosine- and dileucine-based endocytosis signals are recognized by the adaptor complex AP-2. The best understood of these interactions occurs between the tyrosine-based motif, YXX , and the µ2 subunit of AP-2. We recently reported a tryptophan-based endocytosis signal, WLSL, contained within the cytoplasmic domain of the neonatal Fc receptor. This signal resembles YXX . We have investigated the mechanism by which the tryptophan-based signal is recognized. Both interaction assays in vitro and endocytosis assays in vivo show that µ2 binds the tryptophan-based signal. Furthermore, the WLSL sequence binds the same site as YXX . Unlike the WXXF motif, contained in stonin 2 and other endocytic proteins, WLSL does not bind the subunit of AP-2. These observations reveal a functional similarity between the tryptophan-based endocytosis signal and the YXX motif, and an unexpected versatility of µ2 function.
Received for publication, September 17, 2004
, and in revised form, December 7, 2004.
* This work was supported by National Institutes of Health Grant HD27691. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Brandeis University MS 029, Waltham, MA 02254-9110. Tel.: 781-736-4952; Fax: 781-736-2405; E-mail: simister{at}brandeis.edu.

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Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
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