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A role of PI(4,5)P2 for maintaining the activity of TRPC4β : TRPC4β의 활성 유지를 위한 PI(4,5)P2의 역할
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- Authors
- Advisor
- 서인석
- Major
- 의과대학 의과학과
- Issue Date
- 2013-02
- Publisher
- 서울대학교 대학원
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 의과학과 생리학 전공, 2013. 2. 서인석.
- Abstract
- The Transient Receptor Potential Canonical 4 (TRPC4) channel is a Ca2+-permeable, non-selective cation channel in mammalian cells and mediates a number of cellular functions. Our previous study showed that the TRPC4 current was inhibited by co-expression of a constitutively active form of Gq (GqQ209L). It may have caused a shortage of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) because a constitutively active Gq would have persistently activated PLC. Therefore, we used an inducible system to regulate PI(4,5)P2 specifically and acutely. The TRPC4 current was reduced by inducible GqQ209L but not by the mutants whose binding ability to PLC is impaired. Depletion of PI(4,5)P2 using the inositol polyphosphate 5-phosphatase (Inp54p) inducible system led to an irreversible inhibition of TRPC4 currents after application of rapamycin to HEK293 cells that were co-expressing TRPC4 with Inp54p. On the other hand, phosphatidylinositol 4-phosphate 5-kinase (PIP5K) inducible system did not activate the initial gating of TRPC4 channel. Even in the case of Gi2-activated TRPC4 currents, the acute depletion of PI(4,5)P2 led to reduced TRPC4 currents. A PI(4,5)P2 increase, however, did not induce any changes in TRPC4 activation. Therefore, we suggested that PI(4,5)P2 is not the activator for TRPC4 activation but it is still necessary for regulating TRPC4 activation. Especially, TRPC4 desensitization might be a result of hydrolysis of PI(4,5)P2 since TRPC4 desensitization through muscarinic receptor 3 which activates Gq-PLC pathway disappeared by adding PI(4,5)P2 and nonhydrolysis PI(4,5)P2. These findings indicate an essential role of PI(4,5)P2 for maintaining the activity of TRPC4.
* This work is under revision in Pflugers Archiv: European Journal of Physiology (PAEJ-D-12-00300).
- Language
- English
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