?-Fodrin is required for the organization of functional microtubules during mitosis.

ABSTRACT: The cytoskeleton protein ?-fodrin plays a major role in maintaining structural stability of membranes. It was also identified as part of the brain ?-tubulin ring complex, the major microtubule nucleator. Here, we investigated the requirement of ?-fodrin for microtubule spindle assembly during mitotic progression. We found that ?-fodrin depletion results in abnormal mitosis with uncongressed chromosomes, leading to prolonged activation of the spindle assembly checkpoint and a severe mitotic delay. Further, ?-fodrin repression led to the formation of shortened spindles with unstable kinetochore-microtubule attachments. We also found that the mitotic kinesin CENP-E had reduced levels at kinetochores to likely account for the chromosome misalignment defects in ?-fodrin-depleted cells. Importantly, we showed these cells to exhibit reduced levels of detyrosinated ?-tubulin, which primarily drives CENP-E localization. Since proper microtubule dynamics and chromosome alignment are required for completion of normal mitosis, this study reveals an unforeseen role of ?-fodrin in regulating mitotic progression. Future studies on these lines of observations should reveal important mechanistic insight for fodrin's involvement in cancer.

SUBMITTER: Nellikka RK 

PROVIDER: S-EPMC6773225 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature