RRC ID 73839
Author Wang T, Woodman P, Humphrey SJ, Petersen J.
Title Environmental control of Pub1 (NEDD4 family E3 ligase) in Schizosaccharomyces pombe is regulated by TORC2 and Gsk3.
Journal Life Sci Alliance
Abstract Cells respond to changing nutrient environments by adjusting the abundance of surface nutrient transporters and receptors. This can be achieved by modulating ubiquitin-dependent endocytosis, which in part is regulated by the NEDD4 family of E3 ligases. Here we report novel regulation of Pub1, a fission yeast Schizosaccharomyces pombe member of the NEDD4-family of E3 ligases. We show that nitrogen stress inhibits Pub1 function, thereby increasing the abundance of the amino acid transporter Aat1 at the plasma membrane and enhancing sensitivity to the toxic arginine analogue canavanine. We show that TOR complex 2 (TORC2) signalling negatively regulates Pub1, thus TORC2 mutants under nutrient stress have decreased Aat1 at the plasma membrane and are resistant to canavanine. Inhibition of TORC2 signalling increases Pub1 phosphorylation, and this is dependent on Gsk3 activity. Addition of the Tor inhibitor Torin1 increases phosphorylation of Pub1 at serine 199 (S199) by 2.5-fold, and Pub1 protein levels in S199A phospho-ablated mutants are reduced. S199 is conserved in NEDD4 and is located immediately upstream of a WW domain required for protein interaction. Together, we describe how the major TORC2 nutrient-sensing signalling network regulates environmental control of Pub1 to modulate the abundance of nutrient transporters.
Volume 5(5)
Published 2022-5-1
DOI 10.26508/lsa.202101082
PII 5/5/e202101082
PMID 35121625
PMC PMC8817228
MeSH Carbon-Nitrogen Ligases / genetics Carbon-Nitrogen Ligases / metabolism* Glycogen Synthase Kinase 3 / genetics Glycogen Synthase Kinase 3 / metabolism* Mechanistic Target of Rapamycin Complex 2 / metabolism Phosphorylation Protein Serine-Threonine Kinases / metabolism Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Signal Transduction Ubiquitin-Protein Ligases / metabolism
IF 2.622
Yeast FY18665