CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Logarinho, E (Autor) Outra; Maffini, S (Autor) Outra; Barisic, M (Autor) Outra; Marques, A (Autor) Outra; Toso, A (Autor) Outra; Meraldi, P (Autor) Outra; Helder Maiato (Autor) FMUP

Revista

Título: Nature Cell Biology

Vol. 14

Páginas: 295-+

ISSN: 1465-7392

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 62 Citações

Scopus - 65 Citações

Outras Informações

ID Authenticus: P-002-CR2

DOI: 10.1038/ncb2423

Abstract (EN): Loss of spindle-pole integrity during mitosis leads to multipolarity independent of centrosome amplification(1-4). Multipolar-spindle conformation favours incorrect kinetochore microtubule attachments, compromising faithful chromosome segregation and daughter-cell viability(5,6). Spindle-pole organization influences and is influenced by kinetochore activity(7,8), but the molecular nature behind this critical force balance is unknown. CLASPs are microtubule-, kinetochore- and centrosome-associated proteins whose functional perturbation leads to three main spindle abnormalities: monopolarity, short spindles and multipolarity(9-13). The first two reflect a role at the kinetochore microtubule interface through interaction with specific kinetochore partners(10,11,14), but how CLASPs prevent spindle multipolarity remains unclear. Here we found that human CLASPs ensure spindle-pole integrity after bipolarization in response to CENP-E- and Kid-mediated forces from misaligned chromosomes. This function is independent of end-on kinetochore microtubule attachments and involves the recruitment of ninein to residual pericentriolar satellites. Distinctively, multipolarity arising through this mechanism often persists through anaphase. We propose that CLASPs and ninein confer spindle-pole resistance to traction forces exerted during chromosome congression, thereby preventing irreversible spindle multipolarity and aneuploidy.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 17