CLASP1 regulates DYNC1I1 for PLK1-mediated spindle organization and cytokinesis in oocyte meiosis.

Abstract

Meiotic spindle organization and cytokinesis are important for mammalian oocyte maturation. CLIP-associating protein 1 (CLASP1) is a member of the microtubule plus-end-binding proteins that has been reported to regulate cytokinesis in mitosis; however, the functions of CLASP1 in meiosis are still unclear. In this study, we found that CLASP1 plays critical roles both at metaphase and telophase in mouse oocyte meiosis. Our results indicated that CLASP1 is essential for oocyte maturation. Its knockdown caused spindle organization defects and microtubule-kinetochore-attachment defects at metaphase I, which might be due to its association with polo-like kinase 1 (PLK1) and/or phosphorylated mitogen-activated protein kinases (MAPKs), specifically phosphorylated MAPK1 and MAPK3. Furthermore, the levels of deacetylases, i.e. histone deacetylase 6 (HDAC6) and/or NAD-dependent protein deacetylase sirtuin-1 (SIRT1), were found to be increased, which further affected tubulin acetylation levels and microtubule stability after CLASP1 knockdown. We also showed that CLASP1 can associate with PLK1 and/or protein regulator of cytokinesis 1 (PRC1)-based central spindle formation and cytokinesis at telophase I. Moreover, cytoplasmic dynein 1 intermediate chain 1 (DYNC1I1) was recognized to interact closely with CLASP1 and may function as a downstream motor protein involved in the orderly transport of PLK1. Taken together, we demonstrated that CLASP1 may associate with DYNC1I1 to play multiple roles in PLK1-mediated spindle organization and cytokinesis in mouse oocyte meiosis.