The mutual interaction of TRPC5 channel with polycystin proteins

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Misun Kwak Hana Kang Jinhyeong Kim Yejun Hong Byeongseok Jeong Jongyun Myeong Insuk So
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제1호, 93~108쪽, 전체 16쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.01.01

국문 초록

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La3+-induced TRPC5 currents but increased M3R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

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키워드

Polycystic kidney disease 1 protein Polycystic kidney disease 2 protein Polycystic kidney diseases Signal transducer and activator of transcription Transient receptor potential canonical channel 5