Cell-size control

Cells usually grow to a proper size before they divide. To ensure an optimal size for cell survival and function, it is crucial that cells develop efficient and sensitive mechanisms for cell-size control. in 2009, 2 independent studies proposed that the DyRK-family kinase Pom1 could serve as a cell-length sensor to negatively regulate mitotic entry through sAD-like kinase Cdr2 in fission yeast. Pom1 forms concentration gradients with highest concentration at the cell tips. As the cell grows, Pom1 concentration at the cell center decreases continuously until it is too low to maintain the inhibition on Cdr2, whose activation promotes mitotic entry by regulating (directly or indirectly) downstream kinases Cdr1, wee1, and Cdk1. in addition, Pom1 is also a negative regulator of division-site positioning. However, it remains unclear how Pom1 and Cdr2 cooperate in temporal and spatial regulation of cell division. To answer this question, Bhatia et al. 3 set out to further evaluate the Pom1 gradient model on cell-size control and published their work in the February 15, 2014 issue of Cell Cycle. The previous model utilizes Pom1 global protein level along the cell long axis as a cell length indicator. 1,2 However, local protein concentrations define protein functions and behaviors more accurately in a biological process. since Pom1 and Cdr2 concentrate on the plasma membrane, they quantitatively measured Pom1 and Cdr2 fluorescence intensity along the cell cortex. Contrary to the previous model, 1,2 Pom1 level at mid-cortex is much lower and does not change as cells elongate. More surprisingly, the overlap between Pom1 and Cdr2 distribution is small and continues to decrease. 3 These findings contradict the assumptions and predictions in the previous model, where there is a larger Pom1 and Cdr2 overlap, and the Pom1 concentration at cell center decreases during cell growth. Alternatively, the authors provided 3 lines of evidence to show that partial loss of Pom1 protein level or activity, while not affecting division-site positioning, displays premature mitotic entry. 3 Pom1's function in division-site positioning needs much less Pom1 than cell-size control. Temporal regulation on cell division, however, requires higher Pom1 concentration and activity, and is more sensitive to protein level alterations. Cdr2 is the substrate for both Pom1 functions, although Cdr2 only plays a minor role in division-site selection, as anillin Mid1 still forms cytokinesis nodes, and a majority of cells place the division site normally without Cdr2. 4 Pom1 inhibits Cdr2 by phosphorylation on …