Title : Lipid raft segregation modulates
TRPM8 channel activity
Abstract :
- Transient receptor potential channels are a family of cation channels involved in diverse cellular functions
- Most of these channels are expressed in the nervous system and play a key role in sensory physiology
- TRPM8 ( transient receptor potential melastatine 8 ), a member of this family, is activated by cold, cooling substances such menthol and icilin and voltage
- Although TRPM8 is a thermosensitive channel highly expressed in cold sensory neurons, the mechanisms underlying its temperature sensitivity are still poorly understood
- Here we show that, in sensory neurons, TRPM8 channel is localized in cholesterol-rich specialized membrane domains known as lipid rafts
- We also show that, in heterologous expression systems, lipid raft segregation of TRPM8 is favored by glycosylation at the Asn(934) residue of the polypeptide
- In electrophysiological and imaging experiments, using cold and menthol as agonists, we also demonstrate that lipid raft association modulates TRPM8 channel activity
- We found that menthol- and cold-mediated responses of TRPM8 are potentiated when the lipid raft association of the channel is prevented
- In addition, lipid raft disruption shifts the threshold for TRPM8 activation to a warmer temperature
- In view of these data, we suggest a role for lipid rafts in the activity and temperature sensitivity of TRPM8
- We propose a model wherein different lipid membrane environments affect the cold sensing properties of TRPM8 , modulating the response of cold thermoreceptors