Fig. 9. Schematic illustration of TRPC, PKD, and IP3R interaction at the endoplasmic reticulum (ER) and their trafficking to the plasma membrane (PM).
The schematic illustration of the interaction between TRPC and PKD proteins via the ER. TRPC1 and PKD2 function as calcium release channels in the ER. IP3R interacts with both TRPC1 and PKD2 at the ER. The red arrow shows how PKD1 regulates TRPC function. The green arrow shows the process of regulating TRPC through PKD2. The blue arrow shows the signaling process through TRPC. PKD1 acts as a GPCR and activates Gαi proteins. The activated Gαi proteins induced TRPC4 and TRPC5 currents. On the other hand, PKD2 binds to PKD1 and inhibits the activity of PKD1, which lowers the basal activity of G protein and inhibits the basal current and La3+-induced current of TRPC5. Interestingly, when activated through M3R, calcium release through IP3R is added, and the function of PKD2 changes to activating TRPC5 current. This is because PKD2 acts as a calcium-releasing ion channel in the ER, and IP3R further promotes PKD2 function, and vice versa. When TRPC4/5 is activated, calcium is supplied abundantly into the cell, and STAT1 (S701 phosphorylation) and STAT3 (S705 phosphorylation) is activated through the increased calcium and CaMK. STAT phosphorylation might increase the surface expression of PKD2 and TRPC5. TRPC, classical transient receptor potential; PKD, polycystic kidney disease; GPCR, G protein coupled receptor; STAT, signal transducer and activator of transcription.
© Korean J Physiol Pharmacol
