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Compete or Coexist? Why the Same Mechanisms of Symmetry Breaking Can Yield Distinct Outcomes
Article

CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization

1
Department of Mathematics and Department of Mathematical and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8530, Japan
2
Mathematical Institute, University of Oxford, Oxford OX2 6GG, UK
3
Department of Mathematics, The Ohio State University, Columbus, OH 43210, USA
4
Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(9), 2036; https://doi.org/10.3390/cells9092036
Received: 10 August 2020 / Revised: 31 August 2020 / Accepted: 2 September 2020 / Published: 5 September 2020
(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)
Many cells rearrange proteins and other components into spatially distinct domains in a process called polarization. This asymmetric patterning is required for a number of biological processes including asymmetric division, cell migration, and embryonic development. Proteins involved in polarization are highly conserved and include members of the Par and Rho protein families. Despite the importance of these proteins in polarization, it is not yet known how they interact and regulate each other to produce the protein localization patterns associated with polarization. In this study, we develop and analyse a biologically based mathematical model of polarization that incorporates interactions between Par and Rho proteins that are consistent with experimental observations of CDC-42. Using minimal network and eFAST sensitivity analyses, we demonstrate that CDC-42 is predicted to reinforce maintenance of anterior PAR protein polarity which in turn feedbacks to maintain CDC-42 polarization, as well as supporting posterior PAR protein polarization maintenance. The mechanisms for polarity maintenance identified by these methods are not sufficient for the generation of polarization in the absence of cortical flow. Additional inhibitory interactions mediated by the posterior Par proteins are predicted to play a role in the generation of Par protein polarity. More generally, these results provide new insights into the role of CDC-42 in polarization and the mutual regulation of key polarity determinants, in addition to providing a foundation for further investigations. View Full-Text
Keywords: intracellular polarization; partial differential equations; sensitivity analysis intracellular polarization; partial differential equations; sensitivity analysis
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MDPI and ACS Style

Seirin-Lee, S.; Gaffney, E.A.; Dawes, A.T. CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization. Cells 2020, 9, 2036. https://doi.org/10.3390/cells9092036

AMA Style

Seirin-Lee S, Gaffney EA, Dawes AT. CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization. Cells. 2020; 9(9):2036. https://doi.org/10.3390/cells9092036

Chicago/Turabian Style

Seirin-Lee, Sungrim, Eamonn A. Gaffney, and Adriana T. Dawes. 2020. "CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization" Cells 9, no. 9: 2036. https://doi.org/10.3390/cells9092036

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