CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/2036 |
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| author | Sungrim Seirin-Lee Eamonn A. Gaffney Adriana T. Dawes |
| author_facet | Sungrim Seirin-Lee Eamonn A. Gaffney Adriana T. Dawes |
| author_sort | Sungrim Seirin-Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:33:27Z |
| format | Article |
| id | doaj.art-f572d0a1a47043679a093a10480dcb0f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:33:27Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f572d0a1a47043679a093a10480dcb0f2023-11-20T12:43:20ZengMDPI AGCells2073-44092020-09-0199203610.3390/cells9092036CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in PolarizationSungrim Seirin-Lee0Eamonn A. Gaffney1Adriana T. Dawes2Department of Mathematics and Department of Mathematical and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8530, JapanMathematical Institute, University of Oxford, Oxford OX2 6GG, UKDepartment of Mathematics, The Ohio State University, Columbus, OH 43210, USAMany 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.https://www.mdpi.com/2073-4409/9/9/2036intracellular polarizationpartial differential equationssensitivity analysis |
| spellingShingle | Sungrim Seirin-Lee Eamonn A. Gaffney Adriana T. Dawes CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization Cells intracellular polarization partial differential equations sensitivity analysis |
| title | CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization |
| title_full | CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization |
| title_fullStr | CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization |
| title_full_unstemmed | CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization |
| title_short | CDC-42 Interactions with Par Proteins Are Critical for Proper Patterning in Polarization |
| title_sort | cdc 42 interactions with par proteins are critical for proper patterning in polarization |
| topic | intracellular polarization partial differential equations sensitivity analysis |
| url | https://www.mdpi.com/2073-4409/9/9/2036 |
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