Phosphoproteomic identification of Mos-MAPK targets in meiotic cell cycle and asymmetric oocyte divisions.

The Mos kinase activates the ERK/MAPK pathway during oocyte meiosis, controlling essential meiotic functions in species across metazoa. However, despite its significance, the molecular targets of Mos-MAPK remain largely unidentified. Here, we addressed this question using starfish oocytes ideally suited to combine cellular assays with phosphoproteomics. This revealed CPE-mediated mRNA polyadenylation as a prominent target of Mos-MAPK, and we show that translation is required to drive the second meiotic division. Secondly, we identify a well-defined subset of cytoskeletal regulators as targets of Mos-MAPK. We show that this regulation is critical to ensure the asymmetry of meiotic divisions, primarily by reducing the growth of astral microtubules. This allows positioning of the spindle directly beneath the cortex and prevents the separation of spindle poles in anaphase, thereby minimizing polar body size. Thus, by phosphoproteomics, we reveal molecular modules controlled by Mos-MAPK, explaining how this single, conserved kinase can act as a switch between the mitotic and meiotic division programs.