Article
- The EMBO Journal (2004) 23, 4371 - 4383
- doi:10.1038/sj.emboj.7600445
Published online: 21 October 2004
Subject Categories:
Evolving nature of the AP2 
-appendage hub during clathrin-coated vesicle endocytosis
Gerrit JK Praefckeab, Marijn GJ Forda, Eva M Schmid, Lene E Olesen, Jennifer L Gallop, Sew-Yeu Peak-Chew, Yvonne Vallis, M Madan Babu, Ian G Millsc and Harvey T McMahon
- Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
Correspondence to:
Harvey T McMahon, Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, UK. Tel.: +44 1223 402311; Fax: +44 1223 402310; E-mail: hmm@mrc-lmb.cam.ac.uk
aThese authors contributed equally to this work
bPresent address: Zentrum für Molekulare Medizin der Universität Köln, Institut für Genetik, Zülpicher Stra
e 47, 50674 Köln, Germany
cPresent address: The Oncology Department, University of Cambridge Hutchison/MRC Cancer Research Centre, Cambridge CB2 2XZ, UK
Received 18 August 2004; Accepted 21 September 2004
Abstract
Clathrin-mediated endocytosis involves the assembly of a network of proteins that select cargo, modify membrane shape and drive invagination, vesicle scission and uncoating. This network is initially assembled around adaptor protein (AP) appendage domains, which are protein interaction hubs. Using crystallography, we show that FxDxF and WVxF peptide motifs from synaptojanin bind to distinct subdomains on 
-appendages, called 'top' and 'side' sites. Appendages use both these sites to interact with their binding partners in vitro and in vivo. Occupation of both sites simultaneously results in high-affinity reversible interactions with lone appendages (e.g. eps15 and epsin1). Proteins with multiple copies of only one type of motif bind multiple appendages and so will aid adaptor clustering. These clustered (appendage)-hubs have altered properties where they can sample many different binding partners, which in turn can interact with each other and indirectly with clathrin. In the final coated vesicle, most appendage binding partners are absent and thus the functional status of the appendage domain as an interaction hub is temporal and transitory giving directionality to vesicle assembly.
Keywords:
- AP180,
- clathrin-AP2 adaptors,
- eps15,
- epsin1,
- synaptojanin
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