Germ granules are conserved cytoplasmic RNA-protein particles unique to the germline. We have used C. elegans germ granules, known as P granules, as a model system to understand the function and regulation of germ granules during embryonic development. We show that PPTR-1, a regulatory subunit of PP2A, is specifically required for P granule segregation during the asymmetric cell divisions of the germline lineage. In the pptr-1 mutant, we find that germ cells are properly specified despite dramatic P granule segregation defects, indicating that P granule asymmetry is not required for germ cell fate specification. To elucidate the mechanisms of P granule segregation, we have used PPTR-1 as a tool for identification of novel players in P granule segregation. We find PP2APPTR-1 acts downstream of known polarity pathways, and participates in a phosphorylation/dephosphorylation cycle with the kinase MBK-2. This cycle is critical for P granule segregation and asymmetry in the early embryo. The substrates of MBK-2 and PP2APPTR-1, MEG-1 and GEI-12, localize to sub P granular domains scaffolding constitutive P granule components. This work identifies novel regulators of P granule segregation and highlights the crucial role of post-translational modifications on intrinsically disordered proteins in RNA granule assembly.
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Regulation and Function of P granule dynamics during germline development in C. elegans