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Sci. Signal., 27 May 2008
Vol. 1, Issue 21, p. ec199
[DOI: 10.1126/stke.121ec199]

EDITORS' CHOICE

Protein Trafficking Route to Specificity

Annalisa M. VanHook

Science Signaling, AAAS, Washington, DC 20005, USA

In wild-type yeast, rapamycin represses signaling through TORC1, one of two Tor complexes, both of which are localized to endosomal and vacuolar membranes. Rapamycin-mediated TORC1 repression causes dephosphorylation and nuclear translocation of the GATA transcription factor Gln3, inducing transcription of nitrogen catabolite-repressed (NCR) genes. Gln3 also activates NCR genes in yeast transferred to medium containing a poor nitrogen source. Puria et al. (see commentary by Mitchell) report that the nitrogen-limiting and rapamycin signals, both of which are mediated by TORC1, are relayed to Gln3 by distinct mechanisms and that the response to limiting nitrogen conditions depends on Gln3 following a specific route through the cell from Golgi to endosome. In yeast strains that carried a mutation in any one of several genes encoding class C Vps (vacuolar protein sorting) proteins, which are members of a complex that mediates docking and fusion of vesicles with the endosome and vacuole, the response of Gln3 to rapamycin (dephosphorylation, nuclear translocation, and activation of NCR genes) was the same as in wild-type cells, but Gln3 remained cytosolic and NCR genes were not transcribed in response to a shift to low-nitrogen medium. Mutations in class D and, to a lesser extent, class E Vps proteins, all of which are required for Golgi-to-endosome trafficking, phenocopied the class C mutations. In cell fractionation assays of wild-type cell lysates, Gln3 was found in the cytosol and in vesicular, endoplasmic reticulum, and plasma membrane fractions. In class C and D Vps mutants, though, a lesser portion of the Gln3 is detected in the cytosol. Tagged forms of Gln3 and the endosomal marker Vps10 cofractionated from cell lysates and colocalized (by immunocytochemistry) in a punctate pattern consistent with localization to vesicles. Thus, the low-nitrogen transcriptional response mediated by Gln3 appears to rely on specific routing of Gln3 from the Golgi to endosomes, whereas the Gln3-mediated rapamycin response does not share these same trafficking requirements. This implies that TORC1, from its endosomal membrane location, may act on cytoplasmic or endosomal targets specifically. This lends further support to the growing body of evidence that suggests that intracellular vesicles may function as platforms for localizing and concentrating components that confer context specificity to signaling events.

R. Puria, S. A. Zurita-Martinez, M. E. Cardenas, Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 105, 7194-7199 (2008). [Abstract] [Full Text]

A. P. Mitchell, A VAST staging area for regulatory proteins. Proc. Natl. Acad. Sci. U.S.A. 105, 7111-7112 (2008). [Full Text]

Citation: A. M. VanHook, Route to Specificity. Sci. Signal. 1, ec199 (2008).



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