The actin cytoskeleton is a versatile protein polymer that governs cellular processes
including transport, organization and mechanics. We recently found that actin also
protects eggs from chromosomal abnormalities (Mogessie and Schuh, Science, 2017)
that are responsible for nearly 35% of miscarriages and developmental disorders such
as Down syndrome. This was a surprising discovery because chromosomal
organization and dynamics in eukaryotes was thought to rely solely on another
cytoskeletal component, microtubules. It is unknown how functional actin-microtubule
crosstalk is accomplished in eggs to prevent chromosomal abnormalities.
Interestingly, we have now found that actin polymers also exist inside the large nucleus
of healthy mammalian oocytes, before they develop into eggs (Scheffler et al,
bioRxiv,2020). Our data suggest the oocyte nucleus doubles as a homeostatic actin
buffer to prevent assembly of dense cytoplasmic F-actin networks that interfere with
egg development. Importantly, this buffering function may decline with advancing
maternal age, which could provide new molecular clues for generally poor
reproductive outcomes in older women.
In this talk, I will discuss our recent progress, driven by a combination of advanced
microscopy and powerful protein degradation techniques, in understanding how
distinct sub-cellular cytoskeletal ensembles ensure the quality of fertilizable eggs.