FENS-1 and DFCP1 are FYVE domain-containing proteins with distinct functions in the endosomal and Golgi compartments

S H Ridley; N Ktistakis; K Davidson; K E Anderson; M Manifava; C D Ellson; P Lipp; M Bootman; J Coadwell; A Nazarian; H Erdjument-Bromage; P Tempst; M A Cooper; J W Thuring; Z Y Lim; A B Holmes; L R Stephens; P T Hawkins

doi:10.1242/jcs.114.22.3991

FENS-1 and DFCP1 are FYVE domain-containing proteins with distinct functions in the endosomal and Golgi compartments

J Cell Sci. 2001 Nov;114(Pt 22):3991-4000. doi: 10.1242/jcs.114.22.3991.

Authors

S H Ridley¹, N Ktistakis, K Davidson, K E Anderson, M Manifava, C D Ellson, P Lipp, M Bootman, J Coadwell, A Nazarian, H Erdjument-Bromage, P Tempst, M A Cooper, J W Thuring, Z Y Lim, A B Holmes, L R Stephens, P T Hawkins

Affiliation

¹ Inositide Laboratory, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.

PMID: 11739631
DOI: 10.1242/jcs.114.22.3991

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androstadienes / pharmacology
Animals
Brefeldin A / pharmacology
COS Cells
Carrier Proteins / chemistry
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Endosomes / chemistry
Endosomes / drug effects
Endosomes / metabolism*
Enzyme Inhibitors / pharmacology
Golgi Apparatus / drug effects
Golgi Apparatus / metabolism*
Golgi Matrix Proteins
Green Fluorescent Proteins
Humans
Indicators and Reagents / metabolism
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Membrane Lipids / metabolism
Membrane Proteins / metabolism
Phosphatidylinositol Phosphates / metabolism*
Protein Binding
Protein Structure, Tertiary
Protein Synthesis Inhibitors / pharmacology
Protein Transport
Proteins / chemistry
Proteins / genetics
Proteins / metabolism*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Surface Plasmon Resonance
Wortmannin
Zinc Fingers

Substances

Androstadienes
Carrier Proteins
Enzyme Inhibitors
Golgi Matrix Proteins
Indicators and Reagents
Luminescent Proteins
Membrane Lipids
Membrane Proteins
Phosphatidylinositol Phosphates
Protein Synthesis Inhibitors
Proteins
Recombinant Fusion Proteins
ZFYVE1 protein, human
macrogolgin
phosphatidylinositol 3-phosphate
Green Fluorescent Proteins
Brefeldin A
Wortmannin