Quantitative control mechanisms ensure the fidelity of cell division

2017

Challenge

Centrioles are essential organelles that play critical roles in cell division, cell signaling, and cell motility. The number of centrioles in a cell must be strictly maintained, as some human cancers and primary microcephaly can arise when centriole numbers deviate from the norm. How centriole numbers are precisely controlled in healthy cells and what malfunctions lead to unbalanced numbers are not well understood.

Advance

IRP researchers led by Kevin O’Connell, Ph.D., found two protein phosphatases functioning in opposing ways to ensure that numbers of centrioles remain constant from one cell generation to the next. Protein phosphatase 2A promotes expression of the kinase ZYG-1, a master regulator of centriole biogenesis. Loss of protein phosphatase 2A results in the underproduction of centrioles and cell division failure. Conversely, protein phosphatase 1 inhibits the expression of ZYG-1, and the loss of protein phosphatase 1 results in the overproduction of centrioles and abnormal cell division.

Impact

The team’s identification of a novel mechanism that maintains centriole numbers and contributes to the fidelity of cell division, a fundamental biological process that is essential for human health, may lead to new ways of treating diseases that arise due to aberrant centriole numbers.

Publications

Song MH, Liu Y, Anderson DE, Jahng WJ, O'Connell KF. (2011). Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C. elegans by controlling the levels of centriole assembly factors. Dev. Cell. 20(4): 563–571.

Peel N, Iyer J, Naik A, Dougherty MP, Decker M, O'Connell KF. (2017). Protein Phosphatase 1 Down Regulates ZYG-1 Levels to Limit Centriole Duplication. PLoS Genet. 13(1): e1006543.