AP180/CALM Home Page
AP180 is a brain enriched component of clathrin-coated vesicle that is essential for synaptic vesicle recycling. CALM is a ubiquitous homologue.
How it works:
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We have shown that AP180 recruits clathrin to PtdIns(4,5)P2 zones in the membrane and there promotes clathrin polymerisation into 'caps' or domains that approximate to the diameter of a coated vesicle (see background, binding to membranes and polymerisation of clathrin). clathrin-coated caps on a lipid monolayer
Structure of the AP180 N-Terminal Homology (ANTH) domain (see details) structure of CALM ANTH domain bound to PIP2 lipid headgroup
Membrane binding of ANTH domains from AP180 and CALM (see details)

Comparison of the ANTH domain of CALM to the ENTH domain of epsin1 (see details)

Overexpression of AP180 C-terminus leads to the inhibition of all clathrin budding pathways and a tubulation of AP1 positive compartments (see details). Tubulation of AP1 compartments in cells
Major questions still to be answered:
Does AP180 control the size of a clathrin-coated vesicle?
B. Does AP180 function independently of AP2 adaptors to recruit clathrin?

Focus on our publications related to this protein

Ford, M.G.J., Pearse, B., Higgins, M., Vallis, Y., Owen, D., Gibson, A., Hopkins, C.R., Evans, P.R. and McMahon, H.T. (2001) Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 causes nucleation of clathrin lattices on membranes. Science. 291, 1051-1055 (abstract),(pdf). (Also see cover and highlight in same issue)
It was clear to us when we published this paper that the ANTH domain of AP180 was distinct from the ENTH domain of epsin. We discuss this issue further in our Epsin web pages, but in this paper we chose to call this domain AP180-N, and it was not until we had solved the structure of the ENTH domain bound to PtdIns(4,5)P2 that we found the mode of lipid binding was different, and we classified AP180-like proteins as having ANTH domains. Mao et al also published the structure of Drosophila LAP ANTH domain in Cell in the same year (abstract) (pdf).

Stahelin, R. V., Long, F., Peter, B. J., Murray, D., De Camilli, P., McMahon, H. T. and Cho, W. (2003) Contrasting membrane interaction mechanisms of AP180 ANTH and Epsin ENTH domains. J. Biol. Chem. 278(31), 28993-28999. (abstract) (.pdf).

Peter, B.J., Kent, H.M., Mills, I.G., Vallis, Y., Butler, P.J.G., Evans, P.R. and McMahon, H.T. (2003) BAR Domains as Sensors of Membrane Curvature: the Amphiphysin BAR Structure. Science.(pdf)

Marsh, M. and McMahon, H.T. (1999) The Structural Era of Endocytosis. Science 285, 215-220. (abstract) (.pdf)