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

Cell Cycle  2019 August 27 | https://doi.org/10.1080/15384101.2019.1656476  

Rohith Kumar Nellikka, Jamuna S. Sreeja, Dhrishya Dharmapal, Rince John, Augusta Monteiro, Joana Catarina Macedo, Carlos Conde, Elsa Logarinho, Claudio E. Sunkel & Suparna Sengupta

Abstract

The cytoskeleton protein α-fodrin plays a major role in maintaining structural stability of membranes. It was also identified as part of the brain γ-tubulin ring complex, the major microtubule nucleator. Here, we investigated the requirement of α-fodrin for microtubule spindle assembly during mitotic progression. We found that α-fodrin depletion results in abnormal mitosis with uncongressed chromosomes, leading to prolonged activation of the spindle assembly checkpoint and a severe mitotic delay. Further, α-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 α-fodrin-depleted cells. Importantly, we showed these cells to exhibit reduced levels of detyrosinated α-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 α-fodrin in regulating mitotic progression. Future studies on these lines of observations should reveal important mechanistic insight for fodrin's involvement in cancer.

Contact

Rajiv Gandhi Centre for Biotechnology (RGCB),
Thycaud Post, Poojappura,
Thiruvananthapuram - 695 014, Kerala, India
+91-471-2529400 | 2347975 | 2348753
+91-471-2348096
webmaster@rgcb.res.in