title: The exocyst complex binds the small GTPase RalA to mediate filopodia formation.
abstract: The Ras-related small GTPase RalA is involved in controlling actin cytoskeletal remodelling and vesicle transport in mammalian cells. We identified the mammalian homologue of Sec5, a subunit of the exocyst complex determining yeast cell polarity, as a specific binding partner for GTP-ligated RalA. Inhibition of RalA binding to Sec5 prevents filopod production by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and by activated forms of RalA and Cdc42, signalling intermediates downstream of these inflammatory cytokines. We propose that the RalA-exocyst complex interaction integrates the secretory and cytoskeletal pathways.
authors.affiliation: Hematology Division, Department of Medicine, Brigham and women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugihara
authors.forename: Shiro
authors.initials: S
authors.lastname: Asano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Iwamatsu
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Ohta
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020014:K562 Cells; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D033921:Vesicular Transport Proteins; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020725:ral GTP-Binding Proteins
chemical_list: C511410:Exoc2 protein, rat; D007375:Interleukin-1; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; D020558:GTP Phosphohydrolases; C492198:RALA protein, human; C492197:Rala protein, rat; D020764:cdc42 GTP-Binding Protein; D020725:ral GTP-Binding Proteins