title: FENS-1 and DFCP1 are FYVE domain-containing proteins with distinct functions in the endosomal and Golgi compartments.
abstract: FENS-1 and DFCP1 are recently discovered proteins containing one or two FYVE-domains respectively. We show that the FYVE domains in these proteins can bind PtdIns3P in vitro with high specificity over other phosphoinositides. Exogenously expressed FENS-1 localises to early endosomes: this localisation requires an intact FYVE domain and is sensitive to wortmannin inhibition. The isolated FYVE domain of FENS-1 also localises to endosomes. These results are consistent with current models of FYVE-domain function in this cellular compartment. By contrast, exogenously expressed DFCP1 displays a predominantly Golgi, endoplasmic reticulum (ER) and vesicular distribution with little or no overlap with FENS-1 or other endosomal markers. Overexpression of DFCP1 was found to cause dispersal of the Golgi compartment defined by giantin and gpp130-staining. Disruption of the FYVE domains of DFCP1 causes a shift to more condensed and compact Golgi structures and overexpression of this mutant was found to confer significant protection to the Golgi against brefeldin-induced dispersal. These properties of DFCP1 are surprising, and suggest FYVE domain-localisation and function may not be exclusively endosomal. Movies available on-line
authors.affiliation: Inositide Laboratory, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.
authors.forename: S H
authors.initials: SH
authors.lastname: Ridley
authors.forename: N
authors.initials: N
authors.lastname: Ktistakis
authors.forename: K
authors.initials: K
authors.lastname: Davidson
authors.forename: K E
authors.initials: KE
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Manifava
authors.forename: C D
authors.initials: CD
authors.lastname: Ellson
authors.forename: P
authors.initials: P
authors.lastname: Lipp
authors.forename: M
authors.initials: M
authors.lastname: Bootman
authors.forename: J
authors.initials: J
authors.lastname: Coadwell
authors.forename: A
authors.initials: A
authors.lastname: Nazarian
authors.forename: H
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: P
authors.initials: P
authors.lastname: Tempst
authors.forename: M A
authors.initials: MA
authors.lastname: Cooper
authors.forename: J W
authors.initials: JW
authors.lastname: Thuring
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Lim
authors.forename: A B
authors.initials: AB
authors.lastname: Holmes
authors.forename: L R
authors.initials: LR
authors.lastname: Stephens
authors.forename: P T
authors.initials: PT
authors.lastname: Hawkins
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D049452:Green Fluorescent Proteins; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000077191:Wortmannin; D016335:Zinc Fingers
chemical_list: D000730:Androstadienes; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D000077614:Golgi Matrix Proteins; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D008563:Membrane Lipids; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; C426003:ZFYVE1 protein, human; C087574:macrogolgin; C055525:phosphatidylinositol 3-phosphate; D049452:Green Fluorescent Proteins; D020126:Brefeldin A; D000077191:Wortmannin