Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):8002-6. Epub 2003 Jun 13.
Numazaki, M., Tominaga, T., Takeuchi, K., Murayama, N., Toyooka, H., Tominaga, M.,
["Department of Cellular and Molecular Physiology, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan."]
The capsaicin receptor, TRPV1 (VR1), is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. Extracellular Ca2+-dependent desensitization of TRPV1 observed in patch-clamp experiments when using both heterologous expression systems and native sensory ganglia is thought to be one mechanism underlying the paradoxical effectiveness of capsaicin as an analgesic therapy. Here, we show that the Ca2+-binding protein calmodulin binds to a 35-aa segment in the C terminus of TRPV1, and that disruption of the calmodulin-binding segment prevents TRPV1 desensitization. Compounds that interfere with the 35-aa segment could therefore prove useful in the treatment of pain.
Screening
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Experimental screening |
Non-experimental screening |
Reference |
TRP channel construct |
Interactor source |
TRP channel |
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Interactor |
Method |
Species |
Region |
Species |
Organ/tissue |
Sample type |
TRPV1 |
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Calmodulin |
Inference |
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Prediction |
12808128 |
(

:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vitro validation
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Assay with recombinant proteins |
Reference |
TRP channel construct |
Interactor construct |
TRP channel |
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Interactor |
Method |
Species |
Region |
Expression system |
Species |
Region |
Expression system |
TRPV1 |
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Calmodulin |
Fusion protein-pull down assay |
Rat |
C-terminus |
E. coli |
Bovine |
Full-length |
Not specified |
12808128 |
(

:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation
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Assay with endogenous proteins |
Assay with overexpressed proteins |
Reference |
Cell or tissue |
Cell or tissue |
TRP channel construct |
Interactor construct |
TRP channel |
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Interactor |
Method |
Species |
Region |
Species |
Region |
TRPV1 |
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Calmodulin |
Co-immunoprecipitation |
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HEK293 |
Rat |
Full-length |
Rat |
Full-length |
12808128 |
(

:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Characterization
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Binding region mapping |
Stoichiometry |
Affinity (Kd) |
Reference |
TRP channel |
Interactor |
TRP channel |
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Interactor |
Method |
Species |
Region |
Species |
Region |
TRPV1 |
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Calmodulin |
Fusion protein-pull down assay |
Rat |
767-801 |
Bovine |
Not determined |
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|
12808128 |
(

:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Functional consequence
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TRP channel |
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Interactor |
Method |
Post-translational modification |
Subcellular trafficking |
Activity |
Reference |
TRPV1 |
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Calmodulin |
Patch clamp |
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Inhibition |
12808128 |
(

:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)