Classical Transient Receptor Potential 1 (TRPC1): Channel or Channel Regulator?

Abstract

In contrast to other Classical Transient Receptor Potential TRPC channels the function of TRPC1 as an ion channel is a matter of debate, because it is often difficult to obtain substantial functional signals over background in response to over-expression of TRPC1 alone. Along these lines, heterologously expressed TRPC1 is poorly translocated to the plasma membrane as a homotetramer and may not function on its own physiologically, but may rather be an important linker and regulator protein in heteromeric TRPC channel tetramers. However, due to the lack of specific TRPC1 antibodies able to detect native TRPC1 channels in primary cells, identification of functional TRPC1 containing heteromeric TRPC channel complexes in the plasma membrane is still challenging. Moreover, an extended TRPC1 cDNA, which was recently discovered, may seriously question results obtained in heterologous expression systems transfected with shortened cDNA versions. Therefore, this review will focus on the current status of research on TRPC1 function obtained in primary cells and a TRPC1-deficient mouse model.

NADPH oxidases—do they play a role in TRPC regulation under hypoxia?

“…TRPC1 does not fit into this pattern as it might not form functional homotetrameric channels [45,73]. TRPC1 can associate with all TRPC isoforms [45,61,73,97,120,160,161,178,184], as well as with TRP proteins from other TRP sub-families, such as TRPP2, TRPV1, TRPV4 and TRPV6 [50,147]. Moreover, TRPC1 is suggested to assemble with other proteins like Stim1 [125,132] and caveolin-1 [131,140,163].…”

“…TRPC3, TRPC6 and TRPC7 are suggested to assemble and form ROC, gated by diacylglycerol (DAG) derived from C-type phospholipase (PLC)-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) [42]. TRPC1 does not fit into this pattern as it might not form functional homotetrameric channels [45,73]. TRPC1 can associate with all TRPC isoforms [45,61,73,97,120,160,161,178,184], as well as with TRP proteins from other TRP sub-families, such as TRPP2, TRPV1, TRPV4 and TRPV6 [50,147].…”

“…They consist of six transmembrane domains (S1-S6) with a pore-forming unit between domains five and six, four N-terminal ankyrin repeats, a coiled-coil domain for tetrameric assembly and a proline-rich domain (TRP box) with unknown function [73]. In addition, TRPC channels have unique structural features such as a positively charged region and a stromal interaction molecule (STIM)-binding site [45].…”

Transient Receptor Potential (TRP) Channels

“…It appears, based on the current body of scientific research, that different members of this subfamily are activated based on one or both of these two methods depending on the expression system, expression level and the antibody used. Other research has also suggested mechanosensitive gating mechanisms (Dietrich et al 2014). In spite of these experimental limitations, much is known about this subfamily of TRP channels.…”

“…TRPC channels have been shown to form both heterotetramers and homotetramers within the TRP channel superfamily, with different members having certain preferences, for example, TRPC1 forms physiologically relevant functional channels with several TRPC channels including TRPC4, as well as, TRPV1, and TRPP2 (Ong et al 2016; Dietrich et al 2014). …”