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

• 영문명: Negative self-regulation of transient receptor potential canonical 4 by the specific interaction with phospholipase C-δ1
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Juyeon Ko Jinhyeong Kim Jongyun Myeong Misun Kwak Insuk So
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제27권 제2호, 187~196쪽, 전체 10쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2023.03.31

영문 초록

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.

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키워드

Calcium Fluorescence resonance energy transfer Phosphatidylinositols Phospholipase C delta Transient receptor potential channels