The tumour suppressor DLC2 ensures mitotic fidelity by coordinating spindle positioning and cell-cell adhesion

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

JG Ferreira (Autor) FMUP

Revista

Título: Nature Communications

Vol. 5

Páginas: 5826-5826

ISSN: 2041-1723

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 14 Citações

ISI Web of Science

Scopus - 15 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

CORDIS: Ciências Naturais > Ciências biológicas > Biologia > Biologia humana

Outras Informações

ID Authenticus: P-00A-48V

DOI: 10.1038/ncomms6826

Abstract (EN): Dividing epithelial cells need to coordinate spindle positioning with shape changes to maintain cell-cell adhesion. Microtubule interactions with the cell cortex regulate mitotic spindle positioning within the plane of division. How the spindle crosstalks with the actin cytoskeleton to ensure faithful mitosis and spindle positioning is unclear. Here we demonstrate that the tumour suppressor DLC2, a negative regulator of Cdc42, and the interacting kinesin Kif1B coordinate cell junction maintenance and planar spindle positioning by regulating microtubule growth and crosstalk with the actin cytoskeleton. Loss of DLC2 induces the mislocalization of Kif1B, increased Cdc42 activity and cortical recruitment of the Cdc42 effector mDia3, a microtubule stabilizer and promoter of actin dynamics. Accordingly, DLC2 or Kif1B depletion promotes microtubule stabilization, defective spindle positioning, chromosome misalignment and aneuploidy. The tumour suppressor DLC2 and Kif1B are thus central components of a signalling network that guides spindle positioning, cell-cell adhesion and mitotic fidelity.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 15