Protein phosphatase 2A is essential for mitosis and organ development by regulating the stability of the cohesin subunit Verthandi/Rad21 in Drosophila

Abstract

Cohesin is an evolutionarily conserved multi-subunit protein complex involved in sister chromatid cohesion and separation during mitosis. Rad21/Scc1 is an essential subunit of cohesin, but its function and regulation in metazoan development is not well understood. Here, I show that Verthandi (Vtd), the Drosophila homolog of the Scc1 subunit of the cohesin complex, is required for mitosis and organ development depending on the catalytic subunit of PP2A encoded by microtubule star (mts). Double heterozygous mts and vtd mutations show synergistic genetic interaction, resulting in severe mitotic defects during nuclear division cycles in syncytial embryos. Reduction of Mts and Vtd also synergistically impaired mitotic cell division in cellularized embryos. In wing development, double knockdown of Mts and Vtd causes severe reduction of Cut expression, leading to loss of wing margin tissues. Reduction of Mts or Twins (Tws), a regulatory subunit of PP2A, decreased the level of Vtd in wing disc. Inhibition of the proteasome function restored the Vtd level reduced by the inhibition of PP2A and partially suppressed the mitotic defects of mts and vtd heterozygous double mutants. Taken together, this work provides evidence that PP2A is required for the Vtd functions in mitosis and organ growth by directly regulating the Vtd stability through proteasomal degradation pathway.