Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Kelly, Bernard T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Graham, Stephen C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liska, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Dannhauser, Philip N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoening, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ungewickell, Ernst J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Owen, David J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language ADAPTER COMPLEX; COATED VESICLES; PROTEINS; CARGO; RECRUITMENT; PIT; ENDOCYTOSIS; DYNAMIN Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43370