Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange.
The Rab GTPases are key regulators of vesicular transport. A fraction of Rab proteins is present in the cytosol, bound with GDP, complexed to a protein termed GDI. Rab9 is localized primarily to late endosomes, where it aids the transport of mannose 6-phosphate receptors to the trans-Golgi network. It has been proposed that Rab proteins are delivered to specific membranes by GDI, and that this process is accompanied by the exchange of bound GDP for GTP. In addition, Rab localization requires carboxy-terminal prenylation and specific structural determinants. Here we describe the reconstitution of the selective targeting of prenylated Rab9 protein onto late endosome membranes and show that this process is accompanied by endosome-triggered nucleotide exchange.
Soldati
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T
Department of Biochemistry, Stanford University School of Medicine, California 94305-5307.
Shapiro
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AD
Svejstrup
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Pfeffer
S R
SR
D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors; D006150:Guanine Nucleotides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D017368:Protein Prenylation; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D020691:rab GTP-Binding Proteins
C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D006150:Guanine Nucleotides; D017527:Receptor, IGF Type 2; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C489802:Rab9a protein, rat; D020691:rab GTP-Binding Proteins