PMID- 23227176
OWN - NLM
STAT- MEDLINE
DCOM- 20130611
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Regulation of Hxt3 and Hxt7 turnover converges on the Vid30 complex and requires 
      inactivation of the Ras/cAMP/PKA pathway in Saccharomyces cerevisiae.
PG  - e50458
LID - 10.1371/journal.pone.0050458 [doi]
LID - e50458
AB  - Eukaryotic cells adjust their intracellular protein complement as a mechanism to 
      adapt to changing environmental signals. In Saccharomyces cerevisiae the hexose 
      transporters Hxt3 and Hxt7 are expressed and function on the plasma membrane in 
      high and low glucose abundance, respectively. By contrast, Hxt3 is endocytosed 
      and degraded in the vacuole when cells are starved of glucose and Hxt7 in 
      response to rapamycin treatment or when nitrogen is limiting. Yeast uses several 
      signaling pathways, including the TORC1 and Ras/cAMP/Protein Kinase A (PKA) 
      pathways, to adapt to nutrient changes in the environment. The multi-protein 
      Vid30 complex (Vid30c), an E3 ubiquitin ligase required for the degradation of 
      FBPase, assists in this adaptation process in a mechanism that is poorly 
      understood. Here we show the endocytosis and the subsequent degradation of both 
      Hxt3 and Hxt7, in response to different nutrient signals, is dependent on 
      components of the Vid30c. Additionally, we define the signaling events required 
      for the turnover of Hxt3 and Hxt7 by showing that Hxt3 turnover requires Ras2 and 
      PKA inactivation, whereas Hxt7 turnover requires TORC1 and Ras2 inactivation. 
      Further investigation led us to identify Rim15, a kinase that is inhibited by 
      both the TORC1 and Ras/cAMP/PKA pathways, as a key downstream effector in 
      signaling both turnover events. Finally, we show that the turnover of both Hxt3 
      and Hxt7 is dependent on the essential E3 ubiquitin ligase, Rsp5, indicating that 
      the role of the Vid30c might be indirect of Hxt ubiquitylation.
FAU - Snowdon, Chris
AU  - Snowdon C
AD  - Department of Molecular and Cellular Biology, University of Guelph, Guelph, 
      Ontario, Canada.
FAU - van der Merwe, George
AU  - van der Merwe G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121205
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Glucose Transport Proteins, Facilitative)
RN  - 0 (HXT3 protein, S cerevisiae)
RN  - 0 (HXT7 protein, S cerevisiae)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Vesicular Transport Proteins)
RN  - 0 (Vid30 protein, S cerevisiae)
RN  - 3K9958V90M (Ethanol)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Blotting, Western
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Ethanol/pharmacology
MH  - Glucose Transport Proteins, Facilitative/*metabolism
MH  - Microscopy, Fluorescence
MH  - Monosaccharide Transport Proteins/*metabolism
MH  - Saccharomyces cerevisiae/drug effects/*metabolism
MH  - Saccharomyces cerevisiae Proteins/*metabolism
MH  - Ubiquitination
MH  - Vesicular Transport Proteins/*metabolism
MH  - ras Proteins/*metabolism
PMC - PMC3515616
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/12/12 06:00
MHDA- 2013/06/12 06:00
PMCR- 2012/12/05
CRDT- 2012/12/11 06:00
PHST- 2012/07/11 00:00 [received]
PHST- 2012/10/22 00:00 [accepted]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
PHST- 2012/12/05 00:00 [pmc-release]
AID - PONE-D-12-20459 [pii]
AID - 10.1371/journal.pone.0050458 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e50458. doi: 10.1371/journal.pone.0050458. Epub 2012 Dec 5.