Noise Reduction in the Intracellular Pom1p Gradient by a Dynamic Clustering Mechanism

SummaryChemical gradients can generate pattern formation in biological systems. In the fission yeast Schizosaccharomyces pombe, a cortical gradient of pom1p (a DYRK-type protein kinase) functions to position sites of cytokinesis and cell polarity and to control cell length. Here, using quantitative imaging, fluorescence correlation spectroscopy, and mathematical modeling, we study how its gradient distribution is formed. Pom1p gradients exhibit large cell-to-cell variability, as well as dynamic fluctuations in each individual gradient. Our data lead to a two-state model for gradient formation in which pom1p molecules associate with the plasma membrane at cell tips and then diffuse on the membrane while aggregating into and fragmenting from clusters, before disassociating from the membrane. In contrast to a classical one-component gradient, this two-state gradient buffers against cell-to-cell variations in protein concentration. This buffering mechanism, together with time averaging to reduce intrinsic noise, allows the pom1p gradient to specify positional information in a robust manner.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (201 K)Download as PowerPoint slideHighlights► A noisy gradient of pom1p kinase regulates cell size and cytokinesis in S. pombe ► To form a gradient, pom1p binds to membrane at cell tip and diffuses before unbinding ► Pom1p diffuses in dynamic clusters, suggesting a two-state pom1p model ► Cluster formation and time averaging provide mechanisms to suppress noise