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Reference - PMID:34028542 - TORC2 inhibition of α-arrestin Aly3 mediates cell surface persistence of S. pombe Ght5 glucose transporter in low glucose.

Reference summary

PubMed ID
PMID:34028542
Title
TORC2 inhibition of α-arrestin Aly3 mediates cell surface persistence of S. pombe Ght5 glucose transporter in low glucose.
Authors
Toyoda Y, Soejima S, Masuda F, Saitoh S
Citation
J Cell Sci 2021 May 15;134(10)
Publication year
2021
Abstract
In the fission yeast, Schizosaccharomyces pombe, the high-affinity hexose transporter, Ght5, must be transcriptionally upregulated and localized to the cell surface for cell division under limited glucose. Although cell-surface localization of Ght5 depends on Target of rapamycin complex 2 (TORC2), the molecular mechanisms by which TORC2 ensures proper localization of Ght5 remain unknown. We performed genetic screening for gene mutations that restore Ght5 localization on the cell surface in TORC2-deficient mutant cells, and identified a gene encoding an uncharacterized α-arrestin-like protein, Aly3/SPCC584.15c. α-arrestins are thought to recruit a ubiquitin ligase to membrane-associated proteins. Consistently, Ght5 is ubiquitylated in TORC2-deficient cells, and this ubiquitylation is dependent on Aly3. TORC2 supposedly enables cell-surface localization of Ght5 by preventing Aly3-dependent ubiquitylation and subsequent ubiquitylation-dependent translocation of Ght5 to vacuoles. Surprisingly, nitrogen starvation, but not glucose depletion, triggers Aly3-dependent transport of Ght5 to vacuoles in S. pombe, unlike budding yeast hexose transporters, vacuolar transport of which is initiated upon changes in hexose concentration. This study provides new insights into the molecular mechanisms controlling the subcellular localization of hexose transporters in response to extracellular stimuli.

Annotation

GO biological process

GO:0072583 - clathrin-dependent endocytosis

Genes:

GO:0043609 - regulation of carbon utilization

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GO cellular component

GO:0000328 - fungal-type vacuole lumen

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GO:0005886 - plasma membrane

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GO molecular function

GO:1990756 - ubiquitin-like ligase-substrate adaptor activity

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Modification

MOD:01148 - ubiquitinylated lysine

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Multi-locus phenotype

FYPO:0003743 - decreased cell population growth during glucose starvation

Genes:

Genotypes:

FYPO:0000047 - normal cell population growth

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Genotypes:

FYPO:0002674 - normal protein localization to plasma membrane

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Genotypes:

FYPO:0002635 - normal protein ubiquitination during vegetative growth

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Qualitative gene expression

PomGeneEx:0000011 - RNA level increased

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PomGeneEx:0000013 - RNA level unchanged

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Single locus phenotype

FYPO:0004839 - abolished protein localization to plasma membrane, with protein mislocalized to cytoplasm, during glucose starvation

Genes:

Genotypes:

FYPO:0003743 - decreased cell population growth during glucose starvation

Genes:

Genotypes:

FYPO:0002082 - increased protein ubiquitination during vegetative growth

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Genotypes:

FYPO:0000244 - loss of viability upon nutrient depletion

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Genotypes: