Pom1 gradient buffering through intermolecular auto‐phosphorylation

• Published in: Molecular systems biology 2015-07, Vol.11 (7), p.818-n/a
• Main Authors: Hersch, Micha, Hachet, Olivier, Dalessi, Sascha, Ullal, Pranav, Bhatia, Payal, Bergmann, Sven, Martin, Sophie G
• Format: Article
• Language: English
• Subjects: Algorithms; Autocatalysis; auto‐catalysis; Buffers; Cell cycle; cell cycle control; Cell Division; Cell Membrane - metabolism; Concentration gradient; Confidence intervals; Decay; Dephosphorylation; EMBO33; EMBO37; fission yeast Schizosaccharomyces pombe; Fluctuations; gradient formation; Kinases; Localization; Microtubule-Associated Proteins - metabolism; Pattern formation; Phosphorylation; Protein Kinases - chemistry; Protein Kinases - metabolism; Robustness; Schizosaccharomyces - enzymology; Schizosaccharomyces pombe Proteins - metabolism; Spatial data
• ISSN: 1744-4292; 1744-4292
• DOI: 10.15252/msb.20145996

Concentration gradients provide spatial information for tissue patterning and cell organization, and their robustness under natural fluctuations is an evolutionary advantage. In rod‐shaped Schizosaccharomyces pombe cells, the DYRK‐family kinase Pom1 gradients control cell division timing and placement. Upon dephosphorylation by a Tea4‐phosphatase complex, Pom1 associates with the plasma membrane at cell poles, where it diffuses and detaches upon auto‐phosphorylation. Here, we demonstrate that Pom1 auto‐phosphorylates intermolecularly, both in vitro and in vivo , which confers robustness to the gradient. Quantitative imaging reveals this robustness through two system's properties: The Pom1 gradient amplitude is inversely correlated with its decay length and is buffered against fluctuations in Tea4 levels. A theoretical model of Pom1 gradient formation through intermolecular auto‐phosphorylation predicts both properties qualitatively and quantitatively. This provides a telling example where gradient robustness through super‐linear decay, a principle hypothesized a decade ago, is achieved through autocatalysis. Concentration‐dependent autocatalysis may be a widely used simple feedback to buffer biological activities. Synopsis Theoretical modeling and experimental data show that the DYRK‐family kinase Pom1 auto‐phosphorylates intermolecularly. This mechanism confers robustness to Pom1 concentration gradients through super‐linear decay. The DYRK‐family kinase Pom1 auto‐phosphorylates intermolecularly in vivo and in vitro . Quantitative imaging of Pom1 gradient shows gradient robustness through two system's level properties. A theoretical model of Pom1 gradient formation through intermolecular auto‐phosphorylation predicts these properties qualitatively and quantitatively. Thus, Pom1 gradients provide an example of gradient robustness through super‐linear decay. Graphical Abstract Theoretical modeling and experimental data show that the DYRK‐family kinase Pom1 auto‐phosphorylates intermolecularly. This mechanism confers robustness to Pom1 concentration gradients through super‐linear decay.