title: Golgi recruitment of GRIP domain proteins by Arf-like GTPase 1 is regulated by Arf-like GTPase 3.
abstract: Golgins are Golgi-localized proteins present in all molecularly characterized eukaryotes that function in Golgi transport and maintenance of Golgi structure. Some peripheral membrane Golgins, including the yeast Imh1 protein, contain the recently described GRIP domain that can independently mediate Golgi localization by an unknown mechanism. To identify candidate Golgi receptors for GRIP domain proteins, a collection of Saccharomyces cerevisiae deletion mutants was visually screened by using yeast, mouse, and human GFP-GRIP domain fusion proteins for defects in Golgi localization. GFP-GRIP reporters were localized to the cytosol in cells lacking either of two ARF-like (ARL) GTPases, Arl1p and Arl3p. In vitro binding experiments demonstrated that activated Arl1p-GTP binds specifically and directly to the Imh1p GRIP domain. Arl1p colocalized with Imh1p-GRIP at the Golgi, and Golgi localization of Arl1p was regulated by the GTPase cycle of Arl3p. These results suggest a cascade in which the GTPase cycle of Arl3p regulates Golgi localization of Arl1p, which in turn binds to the GRIP domain of Imh1p and recruits it to the Golgi. The similar requirements for localization of GRIP domains from yeast, mouse, and human when expressed in yeast, and the presence of Arl1p and Arl3p homologs in these species, suggest that this is an evolutionarily conserved mechanism.
authors.affiliation: University of Pennsylvania School of Medicine, Department of Cell and Developmental Biology, 421 Curie Boulevard, BRB 2/3, Room 1010, Philadelphia, PA 19104-6058, USA.
authors.forename: Subba Rao Gangi
authors.initials: SR
authors.lastname: Setty
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Shin
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yoshino
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marks
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Burd
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C491310:GRIP1 protein, human; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D029701:Saccharomyces cerevisiae Proteins; C097313:ADP-ribosylation factor related proteins; D020558:GTP Phosphohydrolases; C490248:Arl3 protein, mouse; D020727:ADP-Ribosylation Factors; C490249:ARL3 protein, S cerevisiae; C490247:ARL3 protein, human