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Titolo:
Membrane targeting of a Rab GTPase that fails to associate with Rab escortprotein (REP) or guanine nucleotide dissociation inhibitor (GDI)
Autore:
Overmeyer, JH; Wilson, AL; Maltese, WA;
Indirizzi:
Med Coll Ohio, Dept Biochem & Mol Biol, Toledo, OH 43614 USA Med Coll Ohio Toledo OH USA 43614 iochem & Mol Biol, Toledo, OH 43614 USA Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 23, volume: 276, anno: 2001,
pagine: 20379 - 20386
SICI:
0021-9258(20010608)276:23<20379:MTOARG>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
DENSITY LIPOPROTEIN RECEPTOR; ENDOPLASMIC-RETICULUM; GERANYLGERANYL TRANSFERASE; POSTTRANSLATIONAL MODIFICATION; VESICULAR TRANSPORT; GOLGI COMPARTMENTS; IN-VITRO; BINDING; COMPLEX; FUSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Maltese, WA Med Coll Ohio, Dept Biochem & Mol Biol, 3035 Arlington Ave, Toledo, OH 43614 USA Med Coll Ohio 3035 Arlington Ave Toledo OH USA 43614 43614 USA
Citazione:
J.H. Overmeyer et al., "Membrane targeting of a Rab GTPase that fails to associate with Rab escortprotein (REP) or guanine nucleotide dissociation inhibitor (GDI)", J BIOL CHEM, 276(23), 2001, pp. 20379-20386

Abstract

The targeting of various Rab proteins to different subcellular compartments appears to be determined by variable amino acid sequences located upstream from geranylgeranylated cysteine residues in the C-terminal tail. All nascent Rab proteins are prenylated by geranylgeranyltransferase II, which recognizes the Rab substrate only when it is bound to Rab escort protein (REP), After prenylation, REP remains associated with the modified Rab until it is delivered to the appropriate subcellular membrane. It remains unclear whether docking of the Rab with the correct membrane is solely a function of features contained within the prenylated Rab itself (with REP serving as a "passive" carrier) or whether REP actively participates in the targeting process. To address this issue, we took advantage of a mutation in the alpha2helix of Rab1B (i.e. Y78D) that abolishes REP and GDI interaction without disrupting nucleotide binding or hydrolysis. These studies demonstrate thatreplacing the C-terminal GGCC residues of Rab1B(Y78D) with a CLLL motif permits this protein to be prenylated by geranylgeranyltransferase I but not II both in cell-free enzyme assays and in transfected cells. Subcellular fractionation and immunofluorescence studies reveal that the prenylated Rab1B(Y78D)CLLL, which remains deficient in REP and GDI association is, nonetheless, delivered to the Golgi and endoplasmic reticulum (ER) membranes. When the dominant-negative S22N mutation was inserted into Rab1B-CLLL, the resulting monoprenylated construct suppressed ER --> Golgi protein transport. However, when the Y78D mutation was added to the latter construct, its inhibitory effect on protein trafficking was lost despite the fact that it was localized to the ER/Golgi membrane. Therefore, protein interactions mediated by the alpha2 helical domain of Rab1B(S22N) appear to be essential for its functional interaction with components of the ER --> Golgi transport machinery.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/21 alle ore 03:17:11