Regulation of thermoTRPs by lipids

Figures & data

Figure 1. Chemical structures of lipid molecules that regulate the function of thermoTRPs.

Figure 2. Colesterol interacts with a CRAC motif in the TRPV1 channel. Docking simulation of cholesterol's interactions with the CRAC motif in the S5 transmembrane segment of TRPV1. The cryo-EM structure of TRPV1 in the closed state (PDB 3J5P, chain A) was used and constructed using UCSD-Chimera.

Table 1. Summary of tissue distribution, physiological relevance and lipid regulation of thermoTRP channels.

Channel	Tissue distribution	Physiological relevance	Positive lipid regulation	Negative lipid regulation
TRPA1 (<18°C)	Peripheral sensory neurons, inner ear, ovary, spleen, testis^43,44	Noxious chemical and cold sensation; mechanical and inflammatory thermal hyperalgesia^43,45		PIP2^47 LPC^73
TRPM2 (∼37°C)	Fetal and adult brain, placenta, spleen, heart, bone marrow, liver, leukocytes, lung^49	Heat sensation, glucose-induced insulin secretion;^50 neuronal apoptosis;^80 phagocyte activation; oxidative stress.^27	PIP2^31	LPA^80
TRPM3 (∼40°C)	Somatosensory neurons, pancreas, kidney, brain, pituitary^52	Response to steroids (pregnenolone sulfate); noxious heat^53	PIP2^55	Cholesterol^92,93
TRPM4 (15–35°C)	Liver, kidney, spleen, skeletal muscle, colon, heart, brain, vascular endothelium, prostate, testis^57	Temperature sensation^57	PIP2^61
TRPM5 (15–35°C)	Taste receptor cells, intestine, liver, lung^57	Detection of bitter, sweet, umami tastes; temperature sensation^57	PIP2^63
TRPM8 (<25°C)	Peripheral sensory neurons, smooth muscle, prostate, liver^64	Noxious cold and chemical sensation^64	PIP2^65,67 LPC^71-73	Cholesterol^92, 93
TRPV1 (∼42°C)	Spinal cord, brain, peripheral sensory neurons^8	Noxious chemical and heat sensation; inflammatory thermal hyperalgesia^8	PIP2^11-15,17 LPC^74 LPA^82	PIP2^10,13-15Cholesterol^95 POA^83 RA^84 OA^88
TRPV2 (∼52°C)	Spleen, lung, spinal cord, brain, peripheral sensory neurons^34	Noxious heat sensation^27	PIP2^27,28	LPC^69-71
TRPV3 (31–39°C)	Peripheral sensory spinal cord neurons, skin, tongue, brain^29	Temperature and chemical sensation^29	PIP2^31 Cholesterol^17
TRPV4 (22–42°C)	Brain, liver, fat, kidney, heart, salivary gland, testis, trachea^32	Pressure sensing (DRG), central nervous system osmotic sensing, nociception, warm temperature sensing^32	PIP2^33,34 Cholesterol^91	PIP2^35

The temperatures at which each channel is activated are shown below each channel name. Some lipids are shown as positive and/or negative regulators of channel function due to contrasting experimental results from different research groups. Positive and negative regulation of ion channels include mechanisms where the lipids interact directly with the proteins, membrane trafficking, or signaling pathways affecting the activity of the channels.

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