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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

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

Revista

Título: Cell Cycle

Vol. 18

Páginas: 2713-2726

ISSN: 1538-4101

Editora: Taylor & Francis

Indexação

ISI Web of Knowledge - 1 Citação

Scopus - 3 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14