Abstract
Transient receptor potential canonical (TRPC) channels are the canonical (C) subset of the TRP proteins, which are widely expressed in mammalian cells. They are thought to be primarily involved in determining calcium and sodium entry and have wide-ranging functions that include regulation of cell proliferation, motility and contraction. The channels are modulated by a multiplicity of factors, putatively existing as integrators in the plasma membrane. This review considers the sensitivities of TRPC channels to lipids that include diacylglycerols, phosphatidylinositol bisphosphate, lysophospholipids, oxidized phospholipids, arachidonic acid and its metabolites, sphingosine-1-phosphate, cholesterol and some steroidal derivatives and other lipid factors such as gangliosides. Promiscuous and selective lipid sensing have been detected. There appear to be close working relationships with lipids of the phospholipase C and A2 enzyme systems, which may enable integration with receptor signalling and membrane stretch. There are differences in the properties of each TRPC channel that are further complicated by TRPC heteromultimerization. The lipids modulate activity of the channels or insertion in the plasma membrane. Lipid microenvironments and intermediate sensing proteins have been described that include caveolae, G protein signalling, SEC14-like and spectrin-type domains 1 (SESTD1) and podocin. The data suggest that lipid sensing is an important aspect of TRPC channel biology enabling integration with other signalling systems.
Highlights
There are seven mammalian genes encoding transient receptor potential canonical (TRPC) proteins and all of them except TRPC2 are expressed in humans (Flockerzi 2007, Nilius 2007, Venkatachalam & Montell 2007, Yildirim & Birnbaumer 2007, Abramowitz & Birnbaumer 2008)
This review addresses the topic of TRPC channel sensitivities to lipids as components of specific membrane environments or as active intracellular or intercellular signalling molecules
Identified G protein-coupled receptors for oxidized phospholipids were not involved, suggesting that the effects occurred via a previously unrecognized receptor or independently of receptors, but requiring G protein function. These oxidized phospholipids are amongst the best TRPC5 activators, having an advantage that the activation occurs without complications from Ca2+ release (Al-Shawaf et al 2010)
Summary
1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine is a common component of cell membranes. Its susceptibility to oxidation leads to bioactive oxidation products called oxidized phospholipids, which include 1-palmitoyl-2-oxovaleroyl-phosphatidylcholine (POVPC) and 1-palmitoyl-2-glutaroyl-phosphatidylcholine (PGPC) These lipids constitute a diverse family of signalling lipids that accumulate during oxidative stress, apoptosis and necrosis, and are often associated with inflammatory conditions such as rheumatoid arthritis and atherosclerosis. Identified G protein-coupled receptors for oxidized phospholipids were not involved, suggesting that the effects occurred via a previously unrecognized receptor or independently of receptors, but requiring G protein function. In our experience, these oxidized phospholipids are amongst the best TRPC5 (or TRPC1/5) activators, having an advantage that the activation occurs without complications from Ca2+ release (Al-Shawaf et al 2010)
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