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

• Type: Article in International Scientific Journal
• Date: 2014

Authors

JG Ferreira (Author) FMUP

Journal

Title: Nature Communications

Vol. 5

Pages: 5826-5826

ISSN: 2041-1723

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 14 Citations

ISI Web of Science

Scopus - 15 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

CORDIS: Natural sciences > Biological sciences > Biology > Human biology

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15