Format

Send to

Choose Destination
Mol Cell Biol. 2005 Nov;25(21):9478-90.

Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway.

Author information

1
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

Abstract

In many fungi, transcriptional responses to alkaline pH are mediated by conserved signal transduction machinery. In the homologous system in Saccharomyces cerevisiae, the zinc-finger transcription factor Rim101 is activated under alkaline conditions to regulate transcription of target genes. The activation of Rim101 is exerted through proteolytic processing of its C-terminal inhibitory domain. Regulated processing of Rim101 requires several proteins, including the calpain-like protease Rim13/Cpl1, a putative protease scaffold Rim20, putative transmembrane proteins Rim9, and Rim21/Pal2, and Rim8/Pal3 of unknown biochemical function. To identify new regulatory components and thereby determine the order of action among the components in the pathway, we screened for suppressors of rim9Delta and rim21Delta mutations. Three identified suppressors-did4/vps2, vps24, and vps4-all belonged to "class E" vps mutants, which are commonly defective in multivesicular body sorting. These mutations suppress rim8, rim9, and rim21 but not rim13 or rim20, indicating that Rim8, Rim9, and Rim21 act upstream of Rim13 and Rim20 in the pathway. Disruption of DID4, VPS24, or VPS4, by itself, uncouples pH sensing from Rim101 processing, leading to constitutive Rim101 activation. Based on extensive epistasis analysis between pathway-activating and -inactivating mutations, a model for architecture and regulation of the Rim101 pathway is proposed.

PMID:
16227598
PMCID:
PMC1265799
DOI:
10.1128/MCB.25.21.9478-9490.2005
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center