The cell wall integrity pathway kinase Mpk1 regulates extracellular vesicle production and apoptotic-like vesicle release in Cryptococcus neoformans.

Deleting the cell wall integrity kinase MPK1 in Cryptococcus neoformans increases extracellular vesicle release and shifts EVs toward larger, mannoprotein-decorated-deficient vesicles.

• Why it matters: EV production is environmentally regulated in fungi, but the signaling mechanisms and whether distinct EV populations exist were unclear.
• What they did: A kinase deletion library screen identified CWI pathway kinases MPK1, MKK2, and BCK1 as negative regulators of EV release; cryo-electron microscopy and quantitative proteomics characterized EV size, surface decoration, and proteome remodeling.
• The result: mpk1Δ EVs accumulated larger vesicles, lacked mannoprotein fibrillar decoration, showed reduced capsular polysaccharide association and less protein, depleted GPI-anchored proteins, enriched ribosomal proteins and histones, and displayed apoptotic-like hallmarks including phosphatidylserine exposure under reduced cell viability conditions.