SCF-Fbxo42 promotes synaptonemal complex assembly by downregulating PP2A-B56
Barbosa, P., Zhaunova, L., Debilio, S., Steccanella, V., Kelly, V., Ly, T., Ohkura, H.
The synaptonemal complex promotes faithful exchanges between homologous chromosomes during meiosis. Barbosa et al show that SCF-FBxo42 is important for assembly and maintenance of the synaptonemal complex by restricting the phosphatase PP2A-B56 level.
Summary of Paper by Lori Koch
Meiosis is the specialized cell division that creates gamete cells such as egg and sperm with half the number of chromosomes as somatic cells. The exchange of DNA between homologous chromosome pairs is important for creating genetic diversity and also ensures that chromosomes are segregated and inherited properly. The synaptonemal complex physically links homologous chromosomes during meiosis to ensure pairing and recombination occur correctly. In their recent study published in the Journal of Cell Biology, scientists in Hiro Ohkura’s lab and colleagues led by PhD student Pedro Barbosa uncovered that assembly of the synaptonemal complex is regulated by the E3 ubiquitin ligase SCF associated with the specific F-box proteins SlmbbTRcp and Fbxo42. The work began when a targeted screen in fruit flies identified the SCF complex component SkpA as important for forming a distinctive round, dense structure of DNA and associated proteins observed in fly oocytes called the karyosome. Next, the scientists performed immunoprecipitation followed by mass spectrometry on SkpA and identified 15 F-box proteins associated during oogenesis. The F-box proteins provide specificity to the SCF enzyme complexes, determining which proteins interact to receive the ubiquitin modification. When the researchers used RNA interference to prevent expression of the SkpA-associated F-box proteins Slmb and Fbxo42, they observed defects in synaptonemal complex assembly similar to what was seen when SkpA was lost. To identify substrate proteins, they performed immunoprecipitation and mass spectrometry of Fbxo42 and identified PP2A phosphatase complex. They tracked fluorescent PP2A in cells lacking Fbxo42 and observed a significant increase in the level of PP2A protein. Finally, they genetically over-expressed PP2A and observed synaptonemal complex assembly defects. In sum, the data support a model in which synaptonemal complex assembly requires SCF-Fbxo42 downregulation of PP2A.