Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):8002-6. Epub 2003 Jun 13.

Structural determinant of TRPV1 desensitization interacts with calmodulin.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

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.
PMID: 12808128External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Screening Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vitro validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vivo validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Characterization Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Functional consequence Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b top
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Inference Prediction 12808128
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Screening Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vitro validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vivo validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Characterization Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Functional consequence Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b top
Validation: In vitro validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with recombinant proteins Reference
TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Expression system Species Region Expression system
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Rat C-terminus E. coli Bovine Full-length Not specified 12808128
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Screening Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vitro validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vivo validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Characterization Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Functional consequence Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b top
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Co-immunoprecipitation HEK293 Rat Full-length Rat Full-length 12808128
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Screening Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vitro validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vivo validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Characterization Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Functional consequence Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b top
Characterization Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Binding region mapping Stoichiometry Affinity (Kd) Reference
TRP channel Interactor
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Rat 767-801 Bovine Not determined 12808128
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Screening Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vitro validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vivo validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Characterization Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Functional consequence Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b top
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Patch clamp Inhibition 12808128
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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