title: Oligomers of the ATPase EHD2 confine caveolae to the plasma membrane through       association with actin.
abstract: Caveolae are specialized domains present in the plasma membrane (PM) of most         mammalian cell types. They function in signalling, membrane regulation, and         endocytosis. We found that the Eps-15 homology domain-containing protein 2 (EHD2, an         ATPase) associated with the static population of PM caveolae. Recruitment to the PM         involved ATP binding, interaction with anionic lipids, and oligomerization into         large complexes (60-75S) via interaction of the EH domains with intrinsic         NPF/KPF motifs. Hydrolysis of ATP was essential for binding of EHD2 complexes to         caveolae. EHD2 was found to undergo dynamic exchange at caveolae, a process that         depended on a functional ATPase cycle. Depletion of EHD2 by siRNA or expression of a         dominant-negative mutant dramatically increased the fraction of mobile caveolar         vesicles coming from the PM. Overexpression of EHD2, in turn, caused confinement of         cholera toxin B in caveolae. The confining role of EHD2 relied on its capacity to         link caveolae to actin filaments. Thus, EHD2 likely plays a key role in adjusting         the balance between PM functions of stationary caveolae and the role of caveolae as         vesicular carriers.
authors.affiliation: Institute of Biochemistry, ETH Zurich, Zurich,           Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Stoeber
authors.forename: Ina Karen
authors.initials: IK
authors.lastname: Stoeck
authors.forename: Christine
authors.initials: C
authors.lastname: Hänni
authors.forename: Christopher Karl Ernst
authors.initials: CK
authors.lastname: Bleck
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Balistreri
authors.forename: Ari
authors.initials: A
authors.lastname: Helenius
mesh_terms: D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs
chemical_list: D000199:Actins; D002352:Carrier Proteins; C406446:EHD2 protein, human; D000255:Adenosine Triphosphate