Getting a handle on centrosomes

Centrosomes are required for cytokinesis and are important in cell cycle progression—but how are centrosomes connected to these essential cellular functions at the molecular level? On page 535, Gromley et al. describe the maternal centriole protein centriolin, the first integral centrosome protein linked to both cytokinesis and cell cycle progression in vertebrate cells.

Overexpression, siRNA silencing, or antibody inhibition of centriolin causes an unusual cytokinesis defect, in which cells remain connected by long strands of cytoplasm and form syncytia. Some of the cells later undergo cell cycle arrest in G1/G0, and some undergo apoptosis. The cytokinesis defect is caused by a domain in centriolin that shares homology with yeast regulatory proteins in the MEN/SIN pathway, which controls yeast mitotic exit and cytokinesis.

The results suggest that centriolin links centrosomes to a critical cytokinesis regulatory system and possibly to a cell cycle checkpoint. Screening work is now uncovering additional members of the cytokinesis pathway. Centriolin also contains domains with homology to proteins implicated in human tumorigenesis. Since centrosome defects would cause aneuploidy, a hallmark of cancer, the authors are now trying to determine whether centriolin has oncogenic functions. ▪