title: PRA isoforms are targeted to distinct membrane compartments.
abstract: The prenylated Rab acceptor (PRA) 1 is a protein that binds prenylated Rab GTPases and inhibits their removal from the membrane by GDI. We describe here the isolation of a second isoform that can also bind Rab GTPases in a guanine nucleotide-independent manner. The two PRA isoforms showed distinct intracellular localization with PRA1 localized primarily to the Golgi complex and PRA2 to the endoplasmic reticulum (ER) compartment. The localization signal was mapped to the COOH-terminal domain of the two proteins. A DXEE motif served to target PRA1 to the Golgi. Mutation of any one of the acidic residues within this motif resulted in significant retention of PRA1 in the ER compartment. Moreover, the introduction of a di-acidic motif to the COOH-terminal domain of PRA2 resulted in partial localization to the Golgi complex. The domain responsible for ER localization of PRA2 was also confined to the carboxyl terminus. Our results showed that these sorting signals were primarily responsible for the differential localization of the two PRA isoforms.
authors.affiliation: Loeb Health Research Institute, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9 Canada.
authors.forename: M
authors.initials: M
authors.lastname: Abdul-Ghani
authors.forename: P Y
authors.initials: PY
authors.lastname: Gougeon
authors.forename: D C
authors.initials: DC
authors.lastname: Prosser
authors.forename: L F
authors.initials: LF
authors.lastname: Da-Silva
authors.forename: J K
authors.initials: JK
authors.lastname: Ngsee
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000737:chemistry; D005260:Female; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D017368:Protein Prenylation; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D020691:rab GTP-Binding Proteins