alpha-Tubulin detyrosination impairs mitotic error correction by suppressing MCAK centromeric activity

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Ferreira, LT (Author) Other; Orr, B (Author) Other; Rajendraprasad, G (Author) Other; Pereira, AJ (Author) Other; Lemos, C (Author) Other; Lima, JT (Author) Other; Boldu, CG (Author) Other; J Ferreira (Author) FMUP; Barisic, M (Author) Other; Helder Maiato (Author) FMUP

Journal

Title: Journal of Cell Biology

Vol. 219

ISSN: 0021-9525

Publisher: Rockefeller University Press

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 17 Citations

Other information

Authenticus ID: P-00R-V36

DOI: 10.1083/jcb.201910064

Abstract (EN): Incorrect kinetochore-microtubule attachments during mitosis can lead to chromosomal instability, a hallmark of human cancers. Mitotic error correction relies on the kinesin-13 MCAK, a microtubule depolymerase whose activity in vitro is suppressed by alpha-tubulin detyrosination-a posttranslational modification enriched on long-lived microtubules. However, whether and how MCAK activity required for mitotic error correction is regulated by alpha-tubulin detyrosination remains unknown. Here we found that detyrosinated alpha-tubulin accumulates on correct, more stable, kinetochore-microtubule attachments. Experimental manipulation of tubulin tyrosine ligase (TTL) or carboxypeptidase (Vasohibins-SVBP) activities to constitutively increase alpha-tubulin detyrosination near kinetochores compromised efficient error correction, without affecting overall kinetochore microtubule stability. Rescue experiments indicate that MCAK centromeric activity was required and sufficient to correct the mitotic errors caused by excessive alpha-tubulin detyrosination independently of its global impact on microtubule dynamics. Thus, microtubules are not just passive elements during mitotic error correction, and the extent of alpha-tubulin detyrosination allows centromeric MCAK to discriminate correct vs. incorrect kinetochore-microtubule attachments, thereby promoting mitotic fidelity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 20