A novel mechanism for maintaining spindle normality in mammalian oocytes

Abstract

Mammalian oocyte meiosis holds distinct features from mitosis in many aspects. For example, the organisation of the spindle poles, the separation processes of the chromosomes, the way microtubules (MTs) are nucleated and so forth.¹ Many issues about oocyte meiosis are still to be addressed. Moreover, in the past decade, researchers found that oocyte meiosis in primates, including humans, employed some specific proteins or structures, making the mechanical study of mammalian oocyte meiosis more complicated.^2-4 Among these primate-specific proteins, TUBB8 is the most conspicuous since the Tubb8 mutation in humans accounts for about 30% or more of abnormal clinical cases in MI arrest, fertilisation failure, and early embryo development arrest.^{5, 6} However, there are still many unaddressed questions about TUBB8. For example, what's the exact mechanism by which TUBB8 function to organise and stabilise spindle MTs? Are there effective and easy strategies to rescue all sorts of spindle defects caused by different TUBB8 mutations? Recently, a work by Hui Luo et al has made significant progress on both questions.⁷

For the first question, through a combination of multiple cell biological & molecular biology, and biochemistry techniques, they found that TUBB8-D417N expression significantly disrupted its interaction with EB1, a fundamental MT nucleator and polymerizer, and thereby dis-localised EB1; meanwhile, the EB1 protein level didn't change, suggesting that TUBB8 help the correct localisation of EB1. EB1 mislocalisation in turn seriously disrupted the distribution of several other MT nucleators, including CKAP5 and TACC, but didn't affect their protein levels (Figure 1). In addition, TUBB8-D417N expression also broke up the localisation of several critical MT polymerisers and stabilisers, including TPX2, Ran-GTP and KIF11. All these suggest that TUBB8 is fundamentally important for MT nucleation & polymerisation and the maintenance of spindle bipolarity.

Nonetheless, it's this study that incites the upper issues, and many others. Therefore, it is a very important and enlightening work. It would be exciting to expect further related investigations. Figure 1

Zhi-Xia Yang wrote the manuscript and made the graphic abstract image. Dong Zhang and Zi-Fu Wang proofread and gave advice. All authors read and approved the final manuscript.

The authors declare no conflict of interest.

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