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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
김하나
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 Gq (GqQ209L). It may have caused a shortage of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) because a constitutively active Gq 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 GqQ209L 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 Gi2-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 Gq-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
URI
http://hdl.handle.net/10371/132967
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Master's Degree_의과학과)
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