scholarly journals Complementary α-arrestin - Rsp5 ubiquitin ligase complexes control selective nutrient transporter endocytosis in response to amino acid availability

2020 ◽  
Author(s):  
Vasyl Ivashov ◽  
Johannes Zimmer ◽  
Sinead Schwabl ◽  
Jennifer Kahlhofer ◽  
Sabine Weys ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ubiquitin Ligase ◽  
Amino Acid Transporters ◽  
General Amino Acid Control ◽  
Amino Acid Availability ◽  
Acid Control ◽  
Genome Wide ◽  
A Genome ◽  
Lysine Residues ◽  
Nutrient Transporter

AbstractHow cells adjust transport across their membranes is incompletely understood. Previously, we have shown that S.cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through selective endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that Art2/Ecm21, a member of the α-arrestin family of Rsp5 ubiquitin ligase adaptors, is required for the simultaneous endocytosis of four AATs and induced during starvation by the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in these AATs and instructs Rsp5 to ubiquitinate proximal lysine residues. In response to amino acid excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis of individual AATs. Thus, amino acid availability activates complementary α-arrestin-Rsp5-complexes to control selective endocytosis for nutrient acquisition.

scholarly journals Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Vasyl Ivashov ◽  
Johannes Zimmer ◽  
Sinead Schwabl ◽  
Jennifer Kahlhofer ◽  
Sabine Weys ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ubiquitin Ligase ◽  
Amino Acid Transporters ◽  
General Amino Acid Control ◽  
Amino Acid Availability ◽  
Genome Wide ◽  
A Genome ◽  
Lysine Residues ◽  
Nutrient Transporter

How cells adjust nutrient transport across their membranes is incompletely understood. Previously, we have shown that S. cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that the selective endocytosis of four AATs during starvation required the α-arrestin family protein Art2/Ecm21, an adaptor for the ubiquitin ligase Rsp5, and its induction through the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in AATs and thereby instructs Rsp5 to ubiquitinate proximal lysine residues. When amino acids are in excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis. Thus, amino acid excess or starvation activate complementary α-arrestin-Rsp5-complexes to control selective endocytosis and adapt nutrient acquisition.

scholarly journals The general amino acid control pathway regulates mTOR and autophagy during serum/glutamine starvation

2014 ◽  
Vol 206 (2) ◽  
pp. 173-182 ◽  
Author(s):  
Rui Chen ◽  
Yilong Zou ◽  
Dongxue Mao ◽  
Daxiao Sun ◽  
Guanguang Gao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Amino Acid Level ◽  
Amino Acid Uptake ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
General Amino Acid Control ◽  
Amino Acid Availability ◽  
Acid Control ◽  
Activating Transcription Factor 4

Organisms have evolved elaborate mechanisms to adjust intracellular nutrient levels in response to fluctuating availability of exogenous nutrients. During starvation, cells can enhance amino acid uptake and synthesis through the general amino acid control (GAAC) pathway, whereas nonessential cellular contents are recycled by autophagy. How these two pathways are coordinated in response to starvation is currently unknown. Here we show that the GAAC pathway couples exogenous amino acid availability with autophagy. Starvation caused deactivation of mTOR, which then activated autophagy. In parallel, serum/glutamine starvation activated the GAAC pathway, which up-regulated amino acid transporters, leading to increased amino acid uptake. This elevated the intracellular amino acid level, which in turn reactivated mTOR and suppressed autophagy. Knockdown of activating transcription factor 4, the major transcription factor in the GAAC pathway, or of SLC7A5, a leucine transporter, caused impaired mTOR reactivation and much higher levels of autophagy. Thus, the GAAC pathway modulates autophagy by regulating amino acid uptake and mTOR reactivation during serum/glutamine starvation.

scholarly journals Structure of yeast regulatory geneLEU3and evidence thatLEU3itself is under general amino acid control

1987 ◽  
Vol 15 (13) ◽  
pp. 5261-5273 ◽  
Author(s):  
Kemin Zhou ◽  
Paula R.G. Brisco ◽  
Ari E. Hinkkanen ◽  
Gunter B. Kohlhaw
Keyword(s):  
Amino Acid ◽  
General Amino Acid Control ◽  
Acid Control

scholarly journals Boron Stress Activates the General Amino Acid Control Mechanism and Inhibits Protein Synthesis

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27772 ◽  
Author(s):  
Irem Uluisik ◽  
Alaattin Kaya ◽  
Dmitri E. Fomenko ◽  
Huseyin C. Karakaya ◽  
Bradley A. Carlson ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Control Mechanism ◽  
General Amino Acid Control ◽  
Acid Control

scholarly journals Integration of General Amino Acid Control and Target of Rapamycin (TOR) Regulatory Pathways in Nitrogen Assimilation in Yeast

2010 ◽  
Vol 285 (22) ◽  
pp. 16893-16911 ◽  
Author(s):  
Kirk A. Staschke ◽  
Souvik Dey ◽  
John M. Zaborske ◽  
Lakshmi Reddy Palam ◽  
Jeanette N. McClintick ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nitrogen Assimilation ◽  
Target Of Rapamycin ◽  
Regulatory Pathways ◽  
General Amino Acid Control ◽  
Acid Control

The yeast ILV2 gene is under general amino acid control

Genome ◽  
1988 ◽  
Vol 30 (6) ◽  
pp. 984-986 ◽  
Author(s):  
W. Xiao ◽  
G. H. Rank
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Key Words ◽  
Acetolactate Synthase ◽  
Amino Acid Starvation ◽  
Sulfometuron Methyl ◽  
General Amino Acid Control ◽  
Acid Control ◽  
High Level ◽  
Level Resistance

The yeast ILV2 gene encodes acetolactate synthase, the first enzyme in the biosynthesis of isoleucine and valine. Its multiple regulation has precluded the clear demonstration of whether ILV2 is under general amino acid control. Nonderepressible gcn4 strains were used as recipients for transformation with a YCp plasmid carrying GCN4. Parental gcn4 cells and their isogenic GCN4 transformants were evaluated for ALS derepression following induced amino acid starvation. GCN4 cells showed 1.5-to 1.7-fold derepression but no derepression was observed in isogenic control gcn4 strains. A similar depression of ILV2 mRNA was also observed. Genetic evidence for general amino acid control was the gcn4 suppression of high level resistance to sulfometuron methyl by the SMR1-410 allele of ILV2.Key words: Saccharomyces cerevisiae, ILV2 gene, general amino acid control, multiple regulators.

scholarly journals General amino acid control and specific arginine repression in Saccharomyces cerevisiae: physical study of the bifunctional regulatory region of the ARG3 gene.

1985 ◽  
Vol 5 (11) ◽  
pp. 3139-3148 ◽  
Author(s):  
M Crabeel ◽  
R Huygen ◽  
K Verschueren ◽  
F Messenguy ◽  
K Tinel ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Regulatory Region ◽  
Positive Control ◽  
Posttranscriptional Control ◽  
General Amino Acid Control ◽  
Acid Control ◽  
Physical Study ◽  
Specific Regulation ◽  
General Regulation

To characterize further the regulatory mechanism modulating the expression of the Saccharomyces cerevisiae ARG3 gene, i.e., the specific repression by arginine and the general amino acid control, we analyzed by deletion the region upstream of that gene, determined the nucleotide sequence of operator-constitutive-like mutations affecting the specific regulation, and examined the behavior of an ARG3-galK fusion engineered at the initiating codon of ARG3. Similarly to what was observed in previous studies on the HIS3 and HIS4 genes, our data show that the general regulation acts as a positive control and that a sequence containing the nucleotide TGACTC, between positions -364 and -282 upstream of the transcription start, functions as a regulatory target site. This sequence contains the most proximal of the two TGACTC boxes identified in front of ARG3. While the general control appears to modulate transcription efficiency, the specific repression by arginine displays a posttranscriptional component (F. Messenguy and E. Dubois, Mol. Gen. Genet. 189:148-156, 1983). Our deletion and gene fusion analyses confirm that the specific and general controls operate independently of each other and assign the site responsible for arginine-specific repression to between positions -170 and +22. In keeping with this assignment, the two operator-constitutive-like mutations were localized at positions -80 and -46, respectively, and thus in a region which is not transcribed. We discuss a hypothesis accounting for the involvement of untranscribed DNA in a posttranscriptional control.

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