title: Protein abundance may regulate sensitivity to external cues in polarized cells.
abstract: Cell polarization is a ubiquitous process which results in cellular constituents being organized into discrete intracellular spatial domains. It occurs in a variety of cell types, including epithelial cells, immune system cells and neurons. A key player in this process is the Par protein family whose asymmetric localization to anterior and posterior parts of the cell is crucial for proper division and cell fate specification. In this paper, we explore a stochastic analogue of the temporal model of Par protein interactions first developed in Dawes & Munro (Dawes and Munro 2011 Biophys. J. 101, 1412-1422. (doi:10.1016/j.bpj.2011.07.030)). We focus on how protein abundance influences the behaviour of both the deterministic and stochastic versions of the model. In Dawes & Munro (2011), it was found that bistable behaviour in the temporal model of Par protein led to the existence of complementary domains in the corresponding spatio-temporal model. Here, we find that the corresponding temporal stochastic model permits switching behaviour (the model solution 'jumps' between steady states) for lower protein abundances, whereas for higher protein abundances the stochastic and deterministic models are in good agreement (the model solution evolves to one of two steady states). This led us to the testable hypothesis that cells with lower abundances of Par protein may be more sensitive to external cues, whereas cells with higher abundances of Par protein may be less sensitive to external cues. In order to gain more control over the precise abundance of Par protein, we proposed and explored a second model (again, examining both deterministic and stochastic versions) in which the total number of Par molecules is conserved. We found that this model required an additional dimerization reaction in the cytoplasm in order for bistable and switching behaviour to be found. Once this additional reaction was included, we found that both the first and second models gave qualitatively similar results but in different regions of the parameter space, suggesting a further regulatory mechanism that cells could potentially use to modulate their response to external signals.
authors: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK m.sturrock@imperial.ac.uk.
authors: Marc
authors: M
authors: Sturrock
authors: Department of Mathematics, The Ohio State University, 231 West 18th Avenue, Columbus, OH 43210, USA Department of Molecular Genetics, The Ohio State University, 231 West 18th Avenue, Columbus, OH 43210, USA.
authors: Adriana T
authors: AT
authors: Dawes
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D003198:Computer Simulation; D003463:Cues; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D013347:Subcellular Fractions / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases
keywords: polarization; protein abundance; stochastic model