A phosphatidylinositol (4,5)-bisphosphate binding site within {micro}2-adaptin regulates clathrin-mediated endocytosis

doi:10.1083/jcb.200203103

Published online 15 July 2002. doi:10.1083/jcb.200203103

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© The Rockefeller University Press, 0021-9525/2002/7/209 $5.00
The Journal of Cell Biology, Volume 158, Number 2, July 22, 2002 209-214

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A phosphatidylinositol (4,5)-bisphosphate binding site within µ2-adaptin regulates clathrin-mediated endocytosis

Gundula Rohde¹, Dirk Wenzel² and Volker Haucke¹

¹ Zentrum für Biochemie and Molekulare Zellbiologie, Department of Biochemistry II, University of Göttingen, D-37073 Göttingen, Germany
² Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, D-37077 Göttingen, Germany

Address correspondence to Volker Haucke, Zentrum für Biochemie and Molekulare Zellbiologie, Department of Biochemistry II, University of Göttingen, Humboldtalle 23, D-37073 Göttingen, Germany. Tel.: 49-55-139-9854. Fax: 49-551-39 1-2198. E-mail: vhaucke{at}gwdg.de

The clathrin adaptor complex AP-2 serves to coordinate clathrin-coatedpit assembly with the sorting of transmembrane cargo proteinsat the plasmalemma. How precisely AP-2 assembly and cargo proteinrecognition at sites of endocytosis are regulated has remainedunclear, but recent evidence implicates phosphoinositides, inparticular phosphatidylinositol (4,5)-bisphosphate (PI[4,5]P₂),in these processes. Here we have identified and functionallycharacterized a conserved binding site for PI(4,5)P₂ withinµ2-adaptin, the medium chain of the clathrin adaptor complexAP-2. Mutant µ2 lacking a cluster of conserved lysineresidues fails to bind PI(4,5)P₂ and to compete the recruitmentof native clathrin/AP-2 to PI(4,5)P₂-containing liposomes orto presynaptic membranes. Moreover, we show that expressionof mutant µ2 inhibits receptor-mediated endocytosis inliving cells. We suggest that PI(4,5)P₂ binding to µ2-adaptinregulates clathrin-mediated endocytosis and thereby may contributeto structurally linking cargo recognition to coat formation.

Key Words: clathrin; endocytosis; adaptor; µ2; phosphoinositides

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