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

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Nellikka, RK (Author) Other; Sreeja, JS (Author) Other; Dharmapal, D (Author) Other; John, R (Author) Other; Monteiro, A (Author) Other; Macedo, JC (Author) Other; Conde, C (Author) Other; Logarinho, E (Author) Other; Sunkel, CE (Author) ICBAS; Sengupta, S (Author) Other

Journal

Title: Cell Cycle

Vol. 18

Pages: 2713-2726

ISSN: 1538-4101

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 3 Citations

Other information

Authenticus ID: P-00R-0FQ

DOI: 10.1080/15384101.2019.1656476

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

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14