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Negative self-regulation of transient receptor potential canonical 4 by the specific interaction with phospholipase C-δ1

  • Juyeon Ko (Department of Physiology, Seoul National University College of Medicine) ;
  • Jinhyeong Kim (Department of Physiology, Seoul National University College of Medicine) ;
  • Jongyun Myeong (Department of Physiology, Seoul National University College of Medicine) ;
  • Misun Kwak (Department of Physiology, Seoul National University College of Medicine) ;
  • Insuk So (Department of Physiology, Seoul National University College of Medicine)
  • Received : 2022.11.26
  • Accepted : 2022.12.29
  • Published : 2023.03.01

Abstract

Transient receptor potential canonical (TRPC) channels are non-selective calcium-permeable cation channels. It is suggested that TRPC4β is regulated by phospholipase C (PLC) signaling and is especially maintained by phosphatidylinositol 4,5-bisphosphate (PIP2). In this study, we present the regulation mechanism of the TRPC4 channel with PIP2 hydrolysis which is mediated by a channel-bound PLCδ1 but not by the GqPCR signaling pathway. Our electrophysiological recordings demonstrate that the Ca2+ via an open TRPC4 channel activates PLCδ1 in the physiological range, and it causes the decrease of current amplitude. The existence of PLCδ1 accelerated PIP2 depletion when the channel was activated by an agonist. Interestingly, PLCδ1 mutants which have lost the ability to regulate PIP2 level failed to reduce the TRPC4 current amplitude. Our results demonstrate that TRPC4 self-regulates its activity by allowing Ca2+ ions into the cell and promoting the PIP2 hydrolyzing activity of PLCδ1.

Keywords

Acknowledgement

We thank Jung Eun Lee (Seoul National University, Seoul, Korea) and Christine Haewon Park (Seoul National University, Seoul, Korea) for helpful discussion and proofreading of manuscript. Careful proofreading was done by native speakers of English.

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