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J Biol Chem, Vol. 274, Issue 51, 36153-36158, December 17, 1999

The Leucine-based Sorting Motifs in the Cytoplasmic Domain of the Invariant Chain Are Recognized by the Clathrin Adaptors AP1 and AP2 and their Medium Chains^*

Michael W. Hofmann^§, Stefan Höning^§¶, Dmitrii Rodionov, Bernhard Dobberstein, Kurt von Figura^¶, and Oddmund Bakke^**

From the  Center for Molecular Biology, University of Heidelberg, 69120 Heidelberg, Germany, ^¶ Institute for Biochemistry II, University of Göttingen, 37073 Göttingen, Germany, and  Department of Biology, University of Oslo, N-0316 Oslo, Norway

Recognition of sorting signals within the cytoplasmic tail of membrane proteins by adaptor protein complexes is a crucial step in membrane protein sorting. The three known adaptor complexes, AP1, AP2, and AP3, have all been shown to recognize tyrosine- and leucine-based sorting signals, which are the most common sorting signals within membrane protein cytoplasmic tails. Although tyrosine-based signals are recognized by the µ-chains of adaptor complexes, the subunit recognizing leucine-based sorting signals is less clear.

In this report we show by surface plasmon resonance that the two leucine-based sorting signals within the cytoplasmic tail of the invariant chain bind independently from each other to AP1 and AP2 but not to AP3. We also show that both motifs can be recognized by the µ-chains of AP1 and AP2. Moreover, by using monomeric as well as trimeric invariant chain constructs, we show that adaptor binding does not require trimerization of the invariant chain.

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^* This work was supported by German Science Foundation Grant SFB523, by the Norwegian Cancer Society, and by European Community Grant XCT960058 (to K. v. F. and O. B.).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.

^§ The first two authors contributed equally to this work.

^** To whom correspondence should be addressed: Dept. of Biology, University of Oslo, Box 1050 Blindern, N-0316 Oslo, Norway. Tel.: 47 22855787; Fax: 47 22854605; E-mail: oddmund.bakke@bio.uio.no.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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