K6 Atypical Ubiquitin Chain Regulates Intracellular Serine Homeostasis Through Tor1-Npr1-Par32-Gnp1 Signaling Axis

Area of Science:

• Cellular metabolism
• Molecular biology
• Ubiquitination pathways

Background:

• Intracellular serine homeostasis is vital for cellular functions.
• Mechanisms of serine uptake, biosynthesis, and catalysis require further elucidation.

Purpose of the Study:

• To investigate the role of K6 ubiquitin chains in serine metabolism.
• To identify key proteins and pathways involved in serine homeostasis.

Main Methods:

• Quantitative proteomics to analyze protein expression changes.
• Phenotype assays to assess cellular responses to genetic mutations.
• Investigating protein-protein interactions and post-translational modifications.

Main Results:

• Absence of K6 ubiquitin chains disrupts serine metabolism, reducing biosynthesis and increasing catalytic processes.
• K6R mutant exhibits altered glycerol metabolism and myriocin tolerance, dependent on exogenous serine.
• Gnp1 identified as a key serine transporter, with its uptake regulated by the Tor1-Npr1-Par32 signaling axis.
• K6 ubiquitin chains on Par32 modulate Gnp1 stability and Par32 interaction with Npr1, affecting Gnp1 endocytosis.

Conclusions:

• K6 atypical ubiquitin chains are crucial regulators of serine homeostasis.
• The Tor1-Npr1-Par32-Gnp1 signaling pathway is essential for nutrient sensing and amino acid transporter regulation.