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

ABSTRACT: Proper chromosome segregation is essential to avoid aneuploidy, yet in mammalian oocytes it progressively fails in an age-dependent manner. Proteins contributing to correct chromosome segregation are therefore of central interest. In somatic cells, the scarcely described protein CENP- V was shown to contribute to chromosome structure and segregation, and to microtubule organisation. Here we report a key role for CENP-V in oocyte spindle formation and chromosome segregation. Depending on the maturation state of oocytes CENP-V localizes to and near the centromeres, to MTOCs, and to spindle microtubules. CENP-V deficient oocytes arrest at metaphase I, show strongly reduced polar body extrusion and increased numbers of mis-aligned metaphase I (MI) and metaphase II (MII) chromosomes. Multipolar spindles, unfocused spindle poles and loss of kinetochore spindle fibers illustrate CENP-V’s role in supporting oocyte spindles in MI and MII. Recombinant CENP-V protein binds to, diffuses along, and bundles microtubules in vitro. About half the Cenp-V-/- oocytes arrest at MI in a spindle assembly checkpoint (SAC)- dependent manner. MI arrest, however, only occurs in oocytes from young adults, but fails in oocytes >12 months. This suggests SAC weakening in ageing oocytes allowing them to proceed despite continuous presence of mis-aligned chromosomes. Indeed, an increased rate of aneuploidy is observed in Cenp-V-/- oocytes. Thus, we identified CENP-V as a new microtubule binding protein, crucial to faithful oocyte meiosis, and present Cenp-V-/- oocytes as revealing age-dependent weakening of the SAC.

ORGANISM(S): Mus musculus (mouse)

SUBMITTER: Dalileh Nabi

PROVIDER: S-BSST699 | bioimages |

REPOSITORIES: bioimages

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

Project description: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. Chromosome segregation is essential to avoid aneuploidy, yet in mammalian oocytes it progressively fails in an age-dependent manner. Here the authors identify CENP-V as a microtubule binding and bundling protein crucial to faithful oocyte meiosis, and present Cenp-V−/− oocytes as revealing age-dependent weakening of the spindle assembly checkpoint.

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