Intermediate Filament Protein BFSP2 Controls Spindle Formation via HSC70-Mediated Stabilization of CLTC During Oocyte...

As a major component of the cytoskeleton, intermediate filaments are generally considered to play a supporting role in mitotic cells. They also take part in the regulation of cell motility, proliferation, differentiation, and apoptosis. However, their specific functions during meiosis are largely unknown. Here, a unique role of an intermediate filament protein beaded filament structural protein 2 (BFSP2) is reported, which is predominantly expressed in lens fiber epithelial cells, as a spindle formation controller in oocyte meiosis. BFSP2 is constantly expressed during oocyte meiotic maturation, and specifically distributed on the spindle apparatus at metaphase I (MI) and metaphase II (MII) stages. Depletion of BFSP2 resulted in the meiotic arrest at MI stage due to the aberrant spindle assembly-induced spindle assembly checkpoint activation. Depletion of BFSP2 also led to incorrect kinetochore-microtubule attachments and the occurrence of aneuploidy in oocytes. Mechanistically, immunoprecipitation combined with mass spectrometry analysis identified clathrin heavy chain 1 (CLTC) as the downstream mediator of BFSP2 during meiotic spindle assembly. It is further determined that BFSP2 recruited the molecular chaperone heat shock cognate protein 70 (HSC70) to the spindle apparatus for stabilizing CLTC, and thus driving the spindle formation. In summary, these findings uncover a noncanonical function of the intermediate filament protein BFSP2 as a spindle assembly controller in oocyte meiosis.