Kelly, Bernard T., Graham, Stephen C., Liska, Nicole, Dannhauser, Philip N., Hoening, Stefan, Ungewickell, Ernst J. and Owen, David J. (2014). AP2 controls clathrin polymerization with a membrane-activated switch. Science, 345 (6195). S. 459 - 464. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

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Abstract

Clathrin-mediated endocytosis (CME) is vital for the internalization of most cell-surface proteins. In CME, plasma membrane-binding clathrin adaptors recruit and polymerize clathrin to form clathrin-coated pits into which cargo is sorted. Assembly polypeptide 2 (AP2) is the most abundant adaptor and is pivotal to CME. Here, we determined a structure of AP2 that includes the clathrin-binding beta 2 hinge and developed an AP2-dependent budding assay. Our findings suggest that an autoinhibitory mechanism prevents clathrin recruitment by cytosolic AP2. A large-scale conformational change driven by the plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate and cargo relieves this autoinhibition, triggering clathrin recruitment and hence clathrin-coated bud formation. This molecular switching mechanism can couple AP2's membrane recruitment to its key functions of cargo and clathrin binding.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kelly, Bernard T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graham, Stephen C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liska, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dannhauser, Philip N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoening, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ungewickell, Ernst J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-433709
DOI: 10.1126/science.1254836
Journal or Publication Title: Science
Volume: 345
Number: 6195
Page Range: S. 459 - 464
Date: 2014
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1095-9203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ADAPTER COMPLEX; COATED VESICLES; PROTEINS; CARGO; RECRUITMENT; PIT; ENDOCYTOSIS; DYNAMINMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43370

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