α-Fodrin is required for the organization of functional microtubules during mitosis.
Rohith Kumar NellikkaJamuna S SreejaDhrishya DharmapalRince JohnAugusta MonteiroJoana Catarina MacedoCarlos CondeElsa LogarinhoClaudio E SunkelSuparna SenguptaPublished in: Cell cycle (Georgetown, Tex.) (2019)
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.
Keyphrases
- cell cycle
- induced apoptosis
- cell cycle arrest
- dna damage
- endoplasmic reticulum stress
- copy number
- squamous cell carcinoma
- cell proliferation
- early onset
- small molecule
- binding protein
- genome wide
- oxidative stress
- current status
- mass spectrometry
- white matter
- signaling pathway
- squamous cell
- lymph node metastasis
- subarachnoid hemorrhage
- brain injury
- protein protein