Acetic acid-induced stress granules function as scaffolding complexes for Hog1 activation by Pbs2

Area of Science:

• Cellular stress response
• Signal transduction pathways
• Yeast molecular biology

Background:

• Stress-activated protein kinases (SAPKs) are crucial for cellular response to diverse environmental stressors.
• The precise signaling mechanisms transmitting stress signals to SAPKs are often unidentified.
• The yeast SAPK Hog1 is a key regulator of osmotic stress response.

Purpose of the Study:

• To elucidate the mechanism of acetic acid-induced activation of the yeast SAPK Hog1.
• To investigate the role of stress granules in SAPK activation.
• To determine if acetic acid utilizes the high osmolarity glycerol (HOG) pathway for Hog1 activation.

Main Methods:

• Acetic acid treatment of yeast cells.
• Analysis of Hog1 phosphorylation and localization.
• Stress granule component deletion analysis.
• Co-immunoprecipitation assays to assess protein-protein interactions.

Main Results:

• Acetic acid activates Hog1 through an intracellular mechanism independent of significant HOG pathway stimulation.
• Acetic acid induces the formation of stress granules, which act as scaffolds.
• Stress granules facilitate the stable assembly of Hog1 and its upstream kinase Pbs2.
• This assembly enables Hog1 phosphorylation by leveraging Pbs2's basal activity.
• Stress granule integrity is essential for Hog1 activation and Pbs2 association.
• Activated Hog1 remains localized to stress granules.

Conclusions:

• Stress granules serve as critical platforms for SAPK activation by specific stressors like acetic acid.
• This study reveals a novel mechanism of SAPK activation mediated by stress granule scaffolding.
• The findings suggest stress granules play a role in regulating the localization and function of activated SAPKs.