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Lipid raft segregation modulates TRPM8 channel activity.
Cruz Morenilla-Palao1, María Pertusa, Víctor Meseguer
1Instituto de Neurociencias de Alicante-UMH-CSIC and Unidad de Investigación del Hospital de San Juan de Alicante, San Juan de Alicante 03550, Spain. cruz@umh.es
The Journal of Biological Chemistry
|January 30, 2009
Summary
Lipid rafts modulate the temperature sensitivity of the TRPM8 channel, a key player in cold sensation. Preventing lipid raft association enhances TRPM8 responses to cold and menthol.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- Transient receptor potential (TRP) channels are crucial for cellular functions, particularly sensory physiology in the nervous system.
- TRPM8 (transient receptor potential melastatine 8) is a thermosensitive cation channel activated by cold and menthol, but its temperature sensitivity mechanisms are unclear.
Purpose of the Study:
- To investigate the role of lipid rafts in the localization, activity, and temperature sensitivity of the TRPM8 channel in sensory neurons.
Main Methods:
- Studied TRPM8 localization in sensory neurons and heterologous systems using lipid raft markers.
- Investigated the effect of glycosylation on TRPM8 lipid raft segregation.
- Utilized electrophysiological and imaging techniques with cold and menthol stimulation to assess TRPM8 activity.
Main Results:
- TRPM8 channels are localized within cholesterol-rich lipid rafts in sensory neurons.
- Glycosylation at Asn(934) promotes TRPM8 segregation into lipid rafts.
- Disrupting lipid raft association potentiates TRPM8 responses to cold and menthol and shifts activation thresholds to warmer temperatures.
Conclusions:
- Lipid rafts play a significant role in modulating TRPM8 channel activity and temperature sensitivity.
- Membrane lipid environment influences TRPM8 cold-sensing properties, impacting cold thermoreceptor responses.
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