Reprogramming Cdr2-Dependent Geometry-Based Cell Size Control in Fission Yeast

How cell size is determined and maintained remains unclear, even in simple model organisms. In proliferating cells, cell size is regulated by coordinating growth and division through sizer, adder, or timer mechanisms or through some combination [1, 2]. Currently, the best-characterized example of sizer behavior is in fission yeast, Schizosaccharomyces pombe, which enters mitosis at a minimal cell size threshold. The peripheral membrane kinase Cdr2 localizes in clusters (nodes) on the medial plasma membrane and promotes mitotic entry [3]. Here, we show that the Cdr2 nodal density, which scales with cell size, is used by the cell to sense and control its size. By analyzing cells of different widths, we first show that cdr2⁺ cells divide at a fixed cell surface area. However, division in the cdr2Δ mutant is more closely specified by cell volume, suggesting that Cdr2 is essential for area sensing and supporting the existence of a Cdr2-independent secondary sizer mechanism more closely based on volume. To investigate how Cdr2 nodes may sense area, we derive a minimal mathematical model that incorporates the cytoplasmic kinase Ssp1 as a Cdr2 activator. The model predicts that a cdr2 mutant in an Ssp1 phosphorylation site (cdr2-T166A) [4] should form nodes whose density registers cell length. We confirm this prediction experimentally and find that thin cells now follow this new scaling by dividing at constant length instead of area. This work supports the role of Cdr2 as a sizer factor and highlights the importance of studying geometrical aspects of size control.