The exocyst subunit Sec3 is regulated by a protein quality control pathway

Area of Science:

• Cell Biology
• Molecular Biology
• Protein Degradation

Background:

• Exocytosis is crucial for releasing cellular contents and involves the exocyst complex for vesicle tethering.
• Mechanisms regulating exocyst degradation were previously unknown.
• The exocyst complex is an essential, conserved octameric protein complex.

Purpose of the Study:

• To identify components involved in the degradation pathway of the exocyst complex.
• To elucidate the regulatory mechanisms controlling exocyst subunit turnover.
• To understand the role of protein degradation in exocytosis control.

Main Methods:

• Screening for extragenic suppressors of a temperature-sensitive fission yeast mutant (sec3-913).
• Utilizing gene dosage effects and chemical inhibitors to probe the degradation pathway.
• Investigating the roles of the ubiquitin-proteasome system, molecular chaperones, E3 ligase (Pib1), and deubiquitylating enzyme (Ubp3).

Main Results:

• Exocyst degradation is mediated by the ubiquitin-proteasome system, involving the 26S proteasome subunit Rpt2.
• The degradation pathway is influenced by gene dosage, molecular chaperones (Hsp70), Pib1, and Ubp3.
• Mutations in this pathway alleviated defects in cell septation, exocytosis, and endocytosis in sec3 mutants.
• Wild-type Sec3 degradation is regulated by Pib1 and the 26S proteasome, especially under stress.

Conclusions:

• A cytosolic protein quality control pathway monitors and degrades exocyst subunits via the proteasome.
• This pathway plays a critical role in regulating exocytosis in fission yeast.
• The findings reveal a novel mechanism for controlling exocyst function and cellular secretion.