title: Pom1 gradient buffering through intermolecular auto-phosphorylation.
abstract: 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.
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Micha
authors.initials: M
authors.lastname: Hersch
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hachet
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Sascha
authors.initials: S
authors.lastname: Dalessi
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Pranav
authors.initials: P
authors.lastname: Ullal
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Payal
authors.initials: P
authors.lastname: Bhatia
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland sophie.martin@unil.ch sven.bergmann@unil.ch.
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland sophie.martin@unil.ch sven.bergmann@unil.ch.
authors.forename: Sophie G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D000465:Algorithms; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D029702:Schizosaccharomyces pombe Proteins; C501888:Tea4 protein, S pombe; D011494:Protein Kinases; C112212:Pom1 protein, S pombe
keywords: auto‐catalysis; cell cycle control; fission yeast Schizosaccharomyces pombe; gradient formation; robustness