Differential expression and functionality of TRPA1 protein genetic variants in conditions of thermal stimulation.
The role of genetic modifications of the TRPA1 receptor has been well documented in inflammatory and neuropathic pain. We recently reported that the E179K variant of TRPA1 appears to be crucial for the generation of paradoxical heat sensation in pain patients. Here, we describe the consequences of the single amino acid exchange at position 179 in the ankyrin repeat 4 of human TRPA1. TRPA1 wild type Lys-179 protein expressed in HEK cells exhibited intact biochemical properties, inclusive trafficking into the plasma membrane, formation of large protein complexes, and the ability to be activated by cold. Additionally, a strong increase of Lys-179 protein expression was observed in cold (4 °C) and heat (49 °C)-treated cells. In contrast, HEK cells expressing the variant Lys-179 TRPA1 failed to get activated by cold possibly due to the loss of ability to interact with other proteins or other TRPA1 monomers during oligomerization. In conclusion, the detailed understanding of TRPA1 genetic variants might provide a fruitful strategy for future development of pain treatments.
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Denisa
D
May
Jonas
J
Baastrup
Maria Raphaela
MR
Nientit
Andreas
A
Binder
Michael
M
Schünke
Ralf
R
Baron
Ingolf
I
Cascorbi
D000595:Amino Acid Sequence; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid; D000074025:TRPA1 Cation Channel; D013696:Temperature; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels