title: Pacsin 2 is recruited to caveolae and functions in caveolar biogenesis.
abstract: The pacsin (also termed syndapin) protein family is well characterised structurally. They contain F-BAR domains associated with the generation or maintenance of membrane curvature. The cell biology of these proteins remains less understood. Here, we initially confirm that EHD2, a protein previously shown biochemically to be present in caveolar fractions and to bind to pacsins, is a caveolar protein. We go on to report that GFP-pacsin 2 can be recruited to caveolae, and that endogenous pacsin 2 partially colocalises with caveolin 1 at the plasma membrane. Analysis of the role of pacsin 2 in caveolar biogenesis using small interfering RNA (siRNA) reveals that loss of pacsin 2 function results in loss of morphologically defined caveolae and accumulation of caveolin proteins within the plasma membrane. Overexpression of the F-BAR domain of pacsin 2 (but not the related F-BAR domains of CIP4 and FBP17) disrupts caveolar morphogenesis or trafficking, implying that pacsin 2 interacts with components required for these processes. We propose that pacsin 2 has an important role in the formation of plasma membrane caveolae.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QG, UK.
authors.forename: Carsten Gram
authors.initials: CG
authors.lastname: Hansen
authors.forename: Gillian
authors.initials: G
authors.lastname: Howard
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Nichols
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D021941:Caveolae / Q000502:physiology* / Q000648:ultrastructure; D051242:Caveolin 1 / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D005347:Fibroblasts / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051242:Caveolin 1; D003598:Cytoskeletal Proteins; C406446:EHD2 protein, human; C120714:PACSIN2 protein, human; C485644:Pacsin2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering