NDLI: Protein abundance may regulate sensitivity to external cues in polarized cells

Content Provider	PubMed Central
Author	Sturrock, Marc Dawes, Adriana T.
Copyright Year	2015
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.
Related Links	http://dx.doi.org/10.1098/rsif.2015.0150
Starting Page	20150150
File Format	PDF
ISSN	17425689
e-ISSN	17425662
Journal	Journal of the Royal Society Interface
Issue Number	106
Volume Number	12
Language	English
Publisher	The Royal Society
Publisher Date	2015-04-15
Access Restriction	Open
Rights Holder	The Royal Society
Subject Keyword	Biotechnology Biophysics Biochemistry Bioengineering Biomaterials Biomedical Engineering Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biochemistry Biomaterials Biophysics Bioengineering Biomedical Engineering Biotechnology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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