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

• DOI: 10.1242/jcs.114.22.3991
• Publication Date: 2021-04-26T00:26:59Z
• Authors: 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. J. F. Thuring; Z.-Y. Lim; A. B. Holmes; L. R. Stephens; P. T. Hawkins
• Keywords: FINGER; 571; 572; Green Fluorescent Proteins; FYVE domain; Golgi Apparatus; Endosomes; VESICLES; 1307 Cell Biology; Membrane Lipids; 03 medical and health sciences; Phosphatidylinositol Phosphates; BINDING; Golgi; Animals; Humans; NETWORK; Enzyme Inhibitors; Protein Synthesis Inhibitors; 0303 health sciences; Brefeldin A; PHOSPHATIDYLINOSITOL 3-PHOSPHATE; Golgi Matrix Proteins; Membrane Proteins; LOCALIZATION; PtdIns3P; 3-KINASE; RAB; Protein Structure, Tertiary; Androstadienes; Luminescent Proteins; Protein Transport; endosomes; vesicle trafficking; CELLS; COS Cells; Indicators and Reagents; MEMBRANE; Carrier Proteins; Protein Binding

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