2020年10月30日
A metabolic reaction-diffusion model for PKCα translocation via PIP2 hydrolysis in an endothelial cell.
The Biochemical journal
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- 巻
- 477
- 号
- 20
- 開始ページ
- 4071
- 終了ページ
- 4084
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1042/BCJ20200484
- 出版者・発行元
- PORTLAND PRESS LTD
Hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) at the cell membrane induces the release of inositol 1,4,5-trisphosphate (IP3) into the cytoplasm and diffusion of diacylglycerol (DAG) through the membrane, respectively. Release of IP3 subsequently increases Ca2+ levels in the cytoplasm, which results in activation of protein kinase C α (PKCα) by Ca2+ and DAG, and finally the translocation of PKCα from the cytoplasm to the membrane. In this study, we developed a metabolic reaction-diffusion framework to simulate PKCα translocation via PIP2 hydrolysis in an endothelial cell. A three-dimensional cell model, divided into membrane and cytoplasm domains, was reconstructed from confocal microscopy images. The associated metabolic reactions were divided into their corresponding domain; PIP2 hydrolysis at the membrane domain resulted in DAG diffusion at the membrane domain and IP3 release into the cytoplasm domain. In the cytoplasm domain, Ca2+ was released from the endoplasmic reticulum, and IP3, Ca2+, and PKCα diffused through the cytoplasm. PKCα bound Ca2+ at, and diffused through, the cytoplasm, and was finally activated by binding with DAG at the membrane. Using our model, we analyzed IP3 and DAG dynamics, Ca2+ waves, and PKCα translocation in response to a microscopic stimulus. We found a qualitative agreement between our simulation results and our experimental results obtained by live-cell imaging. Interestingly, our results suggest that PKCα translocation is dominated by DAG dynamics. This three-dimensional reaction-diffusion mathematical framework could be used to investigate the link between PKCα activation in a cell and cell function.
- リンク情報
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- DOI
- https://doi.org/10.1042/BCJ20200484
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/33026061
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000588274400007&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85094982802&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85094982802&origin=inward
- ID情報
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- DOI : 10.1042/BCJ20200484
- ISSN : 0264-6021
- eISSN : 1470-8728
- PubMed ID : 33026061
- SCOPUS ID : 85094982802
- Web of Science ID : WOS:000588274400007