The TRAPP complex mediates secretion arrest induced by stress granule assembly

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The TRAnsport Protein Particle (TRAPP) complex regulates membrane trafficking, crucial for cellular adaptation to stress.
• The integrated stress response (ISR) coordinates cellular defense mechanisms.
• Early secretory pathway dysfunction can impair cellular homeostasis.

Purpose of the Study:

• To investigate the role of the TRAPP complex in the integrated stress response.
• To elucidate the mechanism by which TRAPP influences stress granule formation and function.
• To determine the relationship between TRAPP, COPII, and cell cycle-dependent stress responses.

Main Methods:

• Immunofluorescence microscopy to visualize TRAPP and COPII localization.
• Cell cycle synchronization and CDK1/2 inhibition experiments.
• Western blotting to assess protein interactions and stress granule markers.
• RNA interference (RNAi) to deplete TRAPP complex components.

Main Results:

• TRAPP complex and COPII coat proteins relocate to stress granules (SGs) in cycling cells, dependent on CDK1/2 activity and hnRNPK phosphorylation.
• CDK1/2 inhibition prevents TRAPP/COPII relocation to SGs and stabilizes them at ER exit sites.
• TRAPP depletion results in smaller SGs that fail to recruit RACK1 and Raptor, increasing susceptibility to apoptosis.

Conclusions:

• The TRAPP complex is a key mediator linking the ISR to the early secretory pathway via SG formation.
• CDK1/2-dependent recruitment of TRAPP to SGs regulates Golgi vesiculation and ER export arrest.
• TRAPP complex is essential for SG maturation and cellular stress resistance.