Mogessie, B. | Search bioRxiv

bioRxiv2022

Actin limits egg aneuploidies associated with female reproductive aging.

Aging-related centromeric cohesion loss underlies premature separation of sister chromatids (PSSC) and egg aneuploidy in reproductively older females. Here we show that F-actin maintains chromatid association after cohesion deterioration in aged eggs. F-actin disruption in aged mouse eggs exacerbated PSSC, while its removal in young eggs induced extensive chromatid separation events generally only seen in advanced reproductive ages. In young eggs containing experimentally reduced cohesion, F-actin removal accelerated PSSC in a microtubule dynamics-dependent manner, suggesting that actin counteracts chromatid-pulling spindle forces. Consistently, F-actin stabilization restricted PSSC even when cohesion was acutely depleted by targeted protein degradation. We conclude that actin mitigates PSSCs arising from age-related cohesion depletion by limiting microtubule-driven chromatid separation. This is supported by a spindle-specific disruption of F-actin in aged mammalian eggs. One-Sentence SummaryActin counteracts microtubule-based pulling forces to reduce the effects of chromosome cohesion loss in aged mammalian eggs.

cell biology↗

bioRxiv2020

The prophase oocyte nucleus is a homeostatic G-actin buffer

Formation of healthy mammalian eggs from oocytes requires specialised F-actin structures. F-actin disruption produces aneuploid eggs, which are a leading cause of human embryo deaths, genetic disorders, and infertility. We found that oocytes regulate F-actin organisation and function by promptly transferring excess monomeric G-actin from the cytoplasm to the nucleus. Inside healthy oocyte nuclei, transferred monomers form dynamic F-actin structures, a conserved feature that significantly declines with maternal age. Monomer transfer must be controlled tightly. Blocked nuclear import of G-actin triggers assembly of a dense cytoplasmic F-actin network, while excess G-actin in the nucleus dramatically stabilises nuclear F-actin. Imbalances in either direction predispose oocytes to aneuploidy. The large oocyte nucleus is thus a homeostatic G-actin buffer that is used to maintain cytoplasmic F-actin form and function. One Sentence SummaryMammalian oocyte nuclei buffer cytosolic G-actin

cell biology↗