YeastRGB: comparing the abundance and localization of yeast proteins across cells and libraries

Dubreuil, Benjamin; Sass, Ehud; Nadav, Yotam; Heidenreich, Meta; Georgeson, Joseph M.; Weill, Uri; Duan, Yuanqiang; Meurer, Matthias; Schuldiner, Maya; Knop, Michael; Levy, Emmanuel D.

doi:10.1093/nar/gky941

Cited by 53 publications

(52 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rgd1, a RhoGAP for Rho3 and Rho4, has been shown to localize to polarized vesicles consistent with post-Golgi secretory vesicles (Lefèbvre et al, 2012;Doignon et al, 1999). Rgd2, a RhoGAP for Cdc42 and Rho5, localized to the bud tip in a high-throughput genomic screen (Dubreuil et al, 2018;Roumanie et al, 2001). Here we show that Rgd3 is a RhoGAP for Rho3 and Cdc42, and that it is associated with polarized vesicles.…”

Section: Discussionsupporting

confidence: 62%

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

Gingras

Lwin

Miller

et al. 2020

Preprint

View full text Add to dashboard Cite

Polarized growth requires the integration of polarity pathways with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake. In budding yeast, the myosin-V Myo2 is aided by the kinesin-related protein Smy1 in carrying out the essential Sec4dependent transport of secretory vesicles to sites of polarized growth. Over-expression suppressors of a conditional myo2 smy1 mutant identified a novel F-BAR-containing RhoGAP, Rgd3, that has activity primarily on Rho3, but also Cdc42. Internally tagged Rho3 is restricted to the plasma membrane in a gradient corresponding to cell polarity that is altered upon Rgd3 overexpression. Rgd3 itself is localized to dynamic polarized vesicles that, while distinct from constitutive secretory vesicles, are dependent on actin and Myo2 function. In vitro Rgd3 associates with liposomes in a PIP2-enhanced manner. Further, the Rgd3 C-terminal region contains several phosphorylatable residues within a reported SH3-binding motif. An unphosphorylated mimetic construct is active and highly polarized, while the phospho-mimetic form is not. Rgd3 is capable of activating Myo2, dependent on its phospho-state and Rgd3 overexpression rescues aberrant Rho3 localization and cell morphologies seen at the restrictive temperature in the myo2 smy1 mutant. We propose a model where Rgd3 functions to modulate and maintain Rho3 polarity during growth.

show abstract

Section: Discussionsupporting

confidence: 62%

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

Gingras

Lwin

Miller

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This gene was shown to be induced by Aro80 in the presence of AAAs (21) but its role has never been uncovered. Its cellular localization is not clear according to YeastRGB (26), but one high throughput dataset suggested that Esbp6 is located in the cell periphery (27). Furthermore, an overexpression mutant of ESBP6 was shown to confer tolerance to 6% lactic acid (28).…”

Section: Resultsmentioning

confidence: 99%

Elucidating aromatic acid tolerance at low pH in Saccharomyces cerevisiae using adaptive laboratory evolution

Pereira

Mohamed

Radi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Toxicity from the external presence or internal production of compounds can reduce the growth and viability of microbial cell factories and compromise productivity. Aromatic compounds are generally toxic for microorganisms, which makes their production in microbial hosts challenging. Here we use adaptive laboratory evolution to generate Saccharomyces cerevisiae mutants tolerant to two aromatic acids, coumaric acid and ferulic acid. The evolution experiments were performed at low pH (3.5) to reproduce conditions typical of industrial processes. Mutant strains tolerant to levels of aromatic acids near the solubility limit were then analyzed by whole genome sequencing, which revealed prevalent point mutations in a transcriptional activator (Aro80) that is responsible for regulating the use of aromatic amino acids as the nitrogen source. Among the genes regulated by Aro80, ESBP6 was found to be responsible for increasing tolerance to aromatic acids by exporting them out of the cell. Further examination of the native function of Esbp6 revealed that this transporter can excrete fusel acids (byproducts of aromatic amino acid catabolism) and this role is shared with at least one additional transporter native to S. cerevisiae (Pdr12). Besides conferring tolerance to aromatic acids, ESBP6 overexpression was also shown to significantly improve the secretion in coumaric acid production strains. Overall, we showed that regulating the activity of transporters is a major mechanism to improve tolerance to aromatic acids. These findings can be used to modulate the intracellular concentration of aromatic compounds to optimize the excretion of such products while keeping precursor molecules inside the cell.

show abstract

“…One interesting example is the N-terminal IDR in putative mitochondrial protein SHH3, which we predict to be associated with the mitochondrion, as well as the mitochondrial inner membrane. Indeed, SHH3 assumes what looks to be a mitochondrial localization in recent localization collections such as the LoQAtE (Localization and Quantitation Atlas of the yeast proteomE) database (Breker et al, 2014(Breker et al, , 2013 and Yeast RGB (Dubreuil et al, 2019). Another interesting case is an IDR in MFG1, which FAIDR predicts to be associated with sequence-specific DNA binding ( Figure 4A), indicating that MFG1 could be a transcription factor.…”

Section: Inferring Function For Specific Idrs In Uncharacterized Protmentioning

confidence: 99%

Identifying molecular features that are associated with biological function of intrinsically disordered protein regions

Zarin

Strome

Peng

et al. 2020

Preprint

View full text Add to dashboard Cite

Previously, we showed that intrinsically disordered regions in proteins (IDRs) contain multiple sequence-distributed molecular features that are conserved over evolution, despite little sequence similarity that can be detected in alignments (Zarin et al. 2019). Here, we aim to use these molecular features to make specific functional predictions for individual IDRs and identify the molecular features within them that are responsible for specific functions. We find that the predictable functions are diverse, identifying previously known associated molecular features, as well as features that were previously not known to be associated with these functions. We experimentally confirm that elevated isoelectric point and hydrophobicity, features that are positively associated with mitochondrial localization, are necessary for mitochondrial targeting function. Remarkably, increasing isoelectric point in a synthetic IDR restores weak mitochondrial targeting. We believe feature analysis represents a new systematic approach to understand how biological functions of IDRs are specified by their protein sequences.

show abstract

YeastRGB: comparing the abundance and localization of yeast proteins across cells and libraries

Cited by 53 publications

References 28 publications

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology

Elucidating aromatic acid tolerance at low pH in Saccharomyces cerevisiae using adaptive laboratory evolution

Identifying molecular features that are associated with biological function of intrinsically disordered protein regions

Contact Info

Product

Resources

About