title: Dynamics of a simple regulatory switch.
abstract: We consider the dynamics of a model toggle switch abstracted from the genetic interactions operative in a fungal stress response circuit. The switch transduces an external signal and propagates it forward by mediating the transport between compartments of two interacting gene products. The transport between compartments is assumed to be related to the degree of association between the interacting proteins, a fact for which there exists a wealth of biological evidence. The ubiquity and modularity of this cellular control mechanism warrants a detailed study of the dynamics entailed by various modelling assumptions. Specifically, we consider a general gate model in which both of the associating proteins are freely transportable between compartments. A more restrictive, but biologically supported model, is considered in which only one of the two proteins undergoes transport. Under the strong assumption that the disassociation of the interacting proteins is unidirectional we show that the qualitative dynamics of the two models are similar; that is they both converge to unique periodic orbits. From a biophysical perspective the assumption of unidirectional dissociation is unrealistic. We show that the same result holds for the more restrictive model when one weakens the assumption of unidirectional binding or disassociation. We speculate that this is not true for the more general model. This difference in dynamics may have important biological implications and certainly points to promising avenues of research.
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37232, USA. erik.m.boczko@vanderbilt.edu
authors.forename: Erik
authors.initials: E
authors.lastname: Boczko
authors.forename: Tomás
authors.initials: T
authors.lastname: Gedeon
authors.forename: Konstantin
authors.initials: K
authors.lastname: Mischaikow
mesh_terms: D021581:Active Transport, Cell Nucleus; D008433:Mathematics; D008954:Models, Biological; D009584:Nitrogen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D009584:Nitrogen