Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis

Area of Science:

• Cell Biology
• Molecular Biology
• Plant Biology

Background:

• The exocyst complex is crucial for exocytosis, a fundamental process in all organisms.
• Dysfunction of the exocyst complex is linked to human diseases including diabetes and cancer.
• Studying exocyst regulation in plants like Arabidopsis thaliana is challenging due to severe mutant phenotypes.

Purpose of the Study:

• To investigate the dynamic regulation of exocyst-related processes.
• To identify novel tools for studying exocytosis.
• To explore potential therapeutic targets for exocyst-related diseases.

Main Methods:

• Utilized the small molecule Endosidin2 (ES2).
• Investigated ES2 binding to the EXO70 subunit of the exocyst complex.
• Examined effects of ES2 on exocytosis, endosomal recycling, and vacuolar trafficking in plant and human cells.
• Generated and analyzed an EXO70 mutant with C-terminal truncation for ES2 resistance.

Main Results:

• Endosidin2 (ES2) binds to the EXO70 subunit, inhibiting exocytosis and endosomal recycling in both plant and human cells.
• ES2 enhances vacuolar trafficking in plants.
• A C-terminal truncation of EXO70 confers dominant resistance to ES2, suggesting distinct regulatory roles for the N-terminus.
• ES2 serves as a valuable tool for studying exocytosis.

Conclusions:

• Endosidin2 (ES2) is a potent inhibitor of exocytosis targeting the EXO70 subunit.
• ES2 provides a new chemical probe for dissecting exocytosis and endosomal trafficking pathways.
• The study reveals potential distinct regulatory functions of the EXO70 N-terminus.
• ES2 represents a potential therapeutic target for human diseases associated with exocyst dysfunction.