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

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.

• Authors: Rohith Kumar Nellikka, Jamuna S Sreeja, Dhrishya Dharmapal, Rince John, Augusta Monteiro, Joana Catarina Macedo, Carlos Conde, Elsa Logarinho, Claudio E Sunkel, Suparna Sengupta
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 18 Issue 20 Pg. 2713-2726 (Oct 2019) ISSN: 1551-4005 [Electronic] United States
• PMID: 31455186 (Publication Type: Journal Article)

Chemical References

• Carrier Proteins
• Chromosomal Proteins, Non-Histone
• Microfilament Proteins
• RNA, Small Interfering
• Tubulin
• centromere protein E
• fodrin
• Tyrosine

Topics

• Carrier Proteins (genetics, metabolism)
• Cell Line, Tumor
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• Chromosome Segregation
• Humans
• Kinetochores (metabolism)
• M Phase Cell Cycle Checkpoints (genetics)
• Microfilament Proteins (genetics, metabolism)
• Microtubules (metabolism)
• Mitosis (genetics)
• RNA, Small Interfering
• Spindle Apparatus (metabolism)
• Tubulin (metabolism)
• Tyrosine (metabolism)