PMID: 9450958Apr 4, 1998Paper

Inhibition of endosome fusion by wortmannin persists in the presence of activated Rab5

Molecular Biology of the Cell
A T JonesM J Clague

Abstract

Rab5-dependent endosome fusion is sensitive to the phosphoinositide 3-kinase inhibitor, wortmannin. It has been proposed that phosphoinositide 3-kinase activity may be required for activation of rab5 by influencing its nucleotide cycle such as to promote its active GTP state. In this report we demonstrate that endosome fusion remains sensitive to wortmannin despite preloading of endosomes with stimulatory levels of a GTPase-defective mutant rab5(Q79L) or of a xanthosine triphosphate-binding mutant, rab5(D136N), in the presence of the nonhydrolysable analogue XTPgammaS. These results suggest that activation of rab5 cannot be the principal function of the wortmannin-sensitive factor on the endosome fusion pathway. This result is extrapolated to all GTPases by demonstrating that endosome fusion remains wortmannin sensitive despite prior incubation with the nonhydrolysable nucleotide analogue GTPgammaS. Consistent with these results, direct measurement of clathrin-coated vesicle-stimulated nucleotide dissociation from exogenous rab5 was insensitive to the presence of wortmannin. A large excess of rab5(Q79L), beyond levels required for maximal stimulation of the fusion assay, afforded protection against wortmannin inhibition, and pa...Continue Reading

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Citations

Nov 7, 2008·Protoplasma·B Sönnichsen
Jun 12, 2002·Molecular Biology of the Cell·Tommy W NordengOddmund Bakke
Oct 10, 2008·Molecular Biology of the Cell·Ulf GeumannSilvio O Rizzoli
May 14, 2009·Journal of Experimental Botany·Junqi WangLiwen Jiang
Jun 16, 2005·Journal of Virology·Stephen BerrymanTerry Jackson
May 20, 1999·Molecular Membrane Biology·I G MillsM J Clague
May 20, 1999·Molecular Membrane Biology·K Mohrmann, P van der Sluijs
Aug 8, 2006·Biochemical and Biophysical Research Communications·Marianne BrabecRenate Fuchs
Sep 13, 2005·Cell Metabolism·Françoise KoumanovGeoffrey D Holman
Nov 13, 1999·Nature Cell Biology·S ChristoforidisM Zerial
Jul 23, 2004·Physiological Reviews·Michael G Roth
Apr 23, 2010·The Biochemical Journal·Maya ShvartsmanZ Ioav Cabantchik
Jul 25, 1998·The Journal of Biological Chemistry·M A BarbieriP D Stahl
Jun 11, 1999·The American Journal of Physiology·C PeracchiaL L Peracchia
Jul 13, 2000·Molecular Cell Biology Research Communications : MCBRC·J M Backer
Dec 5, 1998·Biochimica Et Biophysica Acta·M P Wymann, L Pirola

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