title: Functional analysis of Dictyostelium IBARa reveals a conserved role of the I-BAR domain in endocytosis.
abstract: I-BAR (inverse-Bin/amphiphysin/Rvs)-domain-containing proteins such as IRSp53 (insulin receptor substrate of 53 kDa) associate with outwardly curved membranes and connect them to proteins involved in actin dynamics. Research on I-BAR proteins has focussed on possible roles in filopod and lamellipod formation, but their full physiological function remains unclear. The social amoeba Dictyostelium encodes a single I-BAR/SH3 (where SH3 is Src homology 3) protein, called IBARa, along with homologues of proteins that interact with IRSp53 family proteins in mammalian cells, providing an excellent model to study its cellular function. Disruption of the gene encoding IBARa leads to a mild defect in development, but filopod and pseudopod dynamics are unaffected. Furthermore, ectopically expressed IBARa does not induce filopod formation and does not localize to filopods. Instead, IBARa associates with clathrin puncta immediately before they are endocytosed. This role is conserved: human BAIAP2L2 (brain-specific angiogenesis inhibitor 1-associated protein 2-like 2) also tightly co-localizes with clathrin plaques, although its homologues IRSp53 and IRTKS (insulin receptor tyrosine kinase substrate) associate with other punctate structures. The results from the present study suggest that I-BAR-containing proteins help generate the membrane curvature required for endocytosis and implies an unexpected role for IRSp53 family proteins in vesicle trafficking.
authors.affiliation: Beatson Institute for Cancer Research, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Douwe M
authors.initials: DM
authors.lastname: Veltman
authors.forename: Giulio
authors.initials: G
authors.lastname: Auciello
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Spence
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Rappoport
authors.forename: Robert H
authors.initials: RH
authors.lastname: Insall
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D002966:Clathrin; D055504:Insulin Receptor Substrate Proteins; D015800:Protozoan Proteins