The Ubp3/Bre5 deubiquitylation complex modulates COPII vesicle formation

Area of Science:

• Cell Biology
• Molecular Biology
• Protein Trafficking

Background:

• Secretory proteins must be accurately delivered to their subcellular destinations, a process critical for cellular function.
• The endoplasmic reticulum (ER) sorts proteins into COPII vesicles for export, excluding resident and misfolded proteins.
• Previous studies identified yeast mutants with impaired ER export sorting, leading to the secretion of ER-resident proteins like Kar2.

Purpose of the Study:

• To identify novel regulators of ER export by screening for mutations that restore protein sorting stringency in an emp24Δ mutant.
• To investigate the role of the deubiquitylation complex Ubp3/Bre5 in ER protein export and quality control.

Main Methods:

• Utilized the emp24Δ yeast mutant strain, which exhibits defective ER export.
• Employed genetic interaction analysis and live-cell imaging to study protein trafficking.
• Assessed the effect of Ubp3/Bre5 deletion on Kar2 secretion and COPII coat assembly.

Main Results:

• Deletion of the Ubp3/Bre5 complex reversed the Kar2 secretion phenotype in the emp24Δ mutant.
• Loss of Ubp3/Bre5 also corrected protein secretion defects in other ER retention mutants.
• Genetic interactions and imaging data indicated that Ubp3/Bre5 modulates COPII coat assembly at ER exit sites.

Conclusions:

• The Ubp3/Bre5 deubiquitylation complex plays a significant role in regulating ER export.
• Ubp3/Bre5 influences the rate of COPII vesicle formation, impacting ER quality control mechanisms.
• These findings reveal a novel link between deubiquitylation and the regulation of protein trafficking from the ER.