The fission yeast cell size control system integrates pathways measuring cell surface area, volume, and time

Eukaryotic cells tightly control their size, but the relevant aspect of size is unknown in most cases. Fission yeast divide at a threshold cell surface area due in part to the protein kinase Cdr2. We find that fission yeast cells only divide by surface area under a size threshold but shift to volume-based divisions when they reach a larger size. The size threshold for changing from surface area to volume-based control is set by ploidy. Within this size control system, we identified the mitotic activator Cdc25 as a volume-based sizer molecule, while the mitotic cyclin Cdc13 accumulates as a timer. We propose an integrated model for cell size control based on multiple signaling pathways that report on distinct aspects of cell size and growth, including cell surface area (Cdr2), cell volume (Cdc25), and time (Cdc13). Combined modeling and experiments show how this system can generate both sizer and adder-like properties. HIGHLIGHTSO_LIFission yeast use surface area or volume-based cell size control depending on overall size and ploidy C_LIO_LIMitotic activator Cdc25 exhibits properties of a volume-based sizer molecule C_LIO_LIMitotic cyclin Cdc13 accumulates in the nucleus dependent on time, not size C_LIO_LICombined modeling and experiments identify conditions for sizer versus adder behavior C_LI