CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes

Dalileh Nabi, Hauke Drechsler, Johannes Pschirer, Franz Korn, Nadine Schuler, Stefan Diez, Rolf Jessberger () and Mariola Chacón ()
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Dalileh Nabi: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
Hauke Drechsler: B CUBE-Center for Molecular Bioengineering, Technische Universität Dresden
Johannes Pschirer: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
Franz Korn: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
Nadine Schuler: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
Stefan Diez: B CUBE-Center for Molecular Bioengineering, Technische Universität Dresden
Rolf Jessberger: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
Mariola Chacón: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Proper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules. We find that Cenp-V−/− oocytes feature severe deficiencies, including metaphase I arrest, strongly reduced polar body extrusion, increased numbers of mis-aligned chromosomes and aneuploidy, multipolar spindles, unfocused spindle poles and loss of kinetochore spindle fibres. We also show that CENP-V protein binds, diffuses along, and bundles microtubules in vitro. The spindle assembly checkpoint arrests about half of metaphase I Cenp-V−/− oocytes from young adults only. This finding suggests checkpoint weakening in ageing oocytes, which mature despite carrying mis-aligned chromosomes. Thus, CENP-V is a microtubule bundling protein crucial to faithful oocyte meiosis, and Cenp-V−/− oocytes reveal age-dependent weakening of the spindle assembly checkpoint.

Date: 2021
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DOI: 10.1038/s41467-021-26826-3

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