Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Phospholipase C-β3 Mediates the Thrombin-induced Ca2+ Response in Glial Cells

  • Hwang, Jong-Ik (Department of Life Science, Division of Molecular and Life Science Pohang University of Science and Technology) ;
  • Shin, Kum-Joo (Department of Life Science, Division of Molecular and Life Science Pohang University of Science and Technology) ;
  • Oh, Yong-Seok (Department of Life Science, Division of Molecular and Life Science Pohang University of Science and Technology) ;
  • Choi, Jung-Woong (Department of Life Science, Division of Molecular and Life Science Pohang University of Science and Technology) ;
  • Lee, Zee-Won (Biomolecule Research Group, Korea Basic Science Institute) ;
  • Kim, Daesoo (Center for Calcium and Learning, Korea Institute of Science and Technology) ;
  • Ha, Kwon-Soo (Biomolecule Research Group, Korea Basic Science Institute) ;
  • Shin, Hee-Sup (Center for Calcium and Learning, Korea Institute of Science and Technology) ;
  • Ryu, Sung Ho (Department of Life Science, Division of Molecular and Life Science Pohang University of Science and Technology) ;
  • Suh, Pann-Ghill (Department of Life Science, Division of Molecular and Life Science Pohang University of Science and Technology)
  • Received : 2005.01.12
  • Accepted : 2005.01.25
  • Published : 2005.06.30
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Abstract

Phospholipase C-${\beta}$ (PLC-${\beta}$) hydrolyses phosphatidylinositol 4,5-bisphosphate and generates inositol 1,4,5-trisphosphate in response to activation of various G protein-coupled receptors (GPCRs). Using glial cells from knock-out mice lacking either PLC-${\beta}1$ [PLC-${\beta}1$ (-/-)] or PLC-${\beta}3$ [PLC-${\beta}3$ (-/-)], we examined which isotype of PLC-${\beta}$ participated in the cellular signaling events triggered by thrombin. Generation of inositol phosphates (IPs) was enhanced by thrombin in PLC-${\beta}1$ (-/-) cells, but was negligible in PLC-${\beta}3$ (-/-) cells. Expression of PLC-${\beta}3$ in PLC-${\beta}3$ (-/-) cells resulted in an increase in pertussis toxin (PTx)-sensitive IPs in response to thrombin as well as to PAR1-specific peptide, while expression of PLC-${\beta}1$ in PLC-${\beta}1$ (-/-) cells did not have any effect on IP generation. The thrombin-induced $[Ca^{2+}]_i$ increase was delayed and attenuated in PLC-${\beta}3$ (-/-) cells, but normal in PLC-${\beta}1$ (-/-) cells. Pertussis toxin evoked a delayed $[Ca^{2+}]_i$ increase in PLC-${\beta}3$ (-/-) cells as well as in PLC-${\beta}1$ (-/-) cells. These results suggest that activation of PLC-${\beta}3$ by pertussis toxin-sensitive G proteins is responsible for the transient $[Ca^{2+}]_i$ increase in response to thrombin, whereas the delayed $[Ca^{2+}]_i$ increase may be due to activation of some other PLC, such as PLC-${\beta}4$, acting via PTx-insensitive G proteins.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation (KOSEF)

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