A dynamic phosphoproteome reveals stage-specific regulation of cytokinesis in Leishmania

Acute inhibition of MPK2 or MRK1 in axenic Leishmania mexicana amastigotes disrupts spatial coordination of cleavage furrow ingression with nuclear and kinetoplast segregation.

• Why it matters: Developmental remodeling in Leishmania mexicana is linked to poorly defined kinase-driven signalling, and constitutive deletions can mask essential cytokinesis functions.
• What they did: They built a temporal phosphoproteome across seven differentiation time points, profiling 16,495 phosphosites on 3,101 proteins and finding 5,795 dynamically regulated sites, then used analogue-sensitive chemical genetics to inhibit MPK2 or MRK1.
• The result: MPK2 inhibition maps upstream of cytoskeletal remodelling networks and stage-specific MPK2 dependence is shaped by morphology: motile promastigotes tolerate MPK2 inhibition, but loss of flagellar motility sensitises them.

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