title: Cdc42 and ARP2/3-independent regulation of filopodia by an integral membrane lipid-phosphatase-related protein.
abstract: Filopodia are dynamic cell surface protrusions that are required for proper cellular development and function. We report that the integral membrane protein lipid-phosphatase-related protein 1 (LPR1) localizes to and promotes the formation of actin-rich, dynamic filopodia, both along the cell periphery and the dorsal cell surface. Regulation of filopodia by LPR1 was not mediated by cdc42 or Rif, and is independent of the Arp2/3 complex. We found that LPR1 can induce filopodia formation in the absence of the Ena/Vasp family of proteins, suggesting that these molecules are not essential for the development of the protrusions. Mutagenesis experiments identified residues and regions of LPR1 that are important for the induction of filopodia. RNA interference experiments in an ovarian epithelial cancer cell line demonstrated a role for LPR1 in the maintenance of filopodia-like membrane protrusions. These observations, and our finding that LPR1 is a not an active lipid phosphatase, suggest that LPR1 may be a novel integral membrane protein link between the actin core and the surrounding lipid layer of a nascent filopodium.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7090, USA.
authors.forename: Yury J
authors.initials: YJ
authors.lastname: Sigal
authors.forename: Omar A
authors.initials: OA
authors.lastname: Quintero
authors.forename: Richard E
authors.initials: RE
authors.lastname: Cheney
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
mesh_terms: D051377:Actin-Related Protein 2 / Q000378:metabolism*; D051378:Actin-Related Protein 3 / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D016384:Consensus Sequence; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008969:Molecular Sequence Data; D009154:Mutation; D010590:Phalloidine; D010711:Phosphatidate Phosphatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011554:Pseudopodia / Q000378:metabolism*; D012235:Rhodamines; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D005456:Fluorescent Dyes; D012235:Rhodamines; D049452:Green Fluorescent Proteins; D010590:Phalloidine; C112948:lipid phosphate phosphatase; D010711:Phosphatidate Phosphatase; D020764:cdc42 GTP-Binding Protein