α-Fodrin is required for the organization of functional microtubules during mitosis.
Cell Cycle
; 18(20): 2713-2726, 2019 Oct.
Article
in En
| MEDLINE
| ID: mdl-31455186
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomal Proteins, Non-Histone
/
Carrier Proteins
/
M Phase Cell Cycle Checkpoints
/
Microfilament Proteins
/
Microtubules
/
Mitosis
Limits:
Humans
Language:
En
Journal:
Cell Cycle
Year:
2019
Document type:
Article
Affiliation country:
India