J Biol Chem. 2001 Jun 15;276(24):21303-10. Epub 2001 Apr 4.

Identification of common binding sites for calmodulin and inositol 1,4,5-trisphosphate receptors on the carboxyl termini of trp channels.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Tang, J., Lin, Y., Zhang, Z., Tikunova, S., Birnbaumer, L., Zhu, M. X.,
["Neurobiotechnology Center, Department of Neuroscience, Ohio State University, Columbus, Ohio 43210, USA."]
Homologues of Drosophila Trp (transient receptor potential) form plasma membrane channels that mediate Ca(2+) entry following the activation of phospholipase C by cell surface receptors. Among the seven Trp homologous found in mammals, Trp3 has been shown to interact with and respond to IP(3) receptors (IP(3)Rs) for activation. Here we show that Trp4 and other Trp proteins also interact with IP(3)Rs. The IP(3)R-binding domain also interacts with calmodulin (CaM) in a Ca(2+)-dependent manner with affinities ranging from 10 nm for Trp2 to 290 nm for Trp6. In addition, other binding sites for CaM and IP(3)Rs are present in the alpha but not the beta isoform of Trp4. In the presence of Ca(2+), the Trp-IP(3)R interaction is inhibited by CaM. However, a synthetic peptide representing a Trp-binding domain of IP(3)Rs inhibited the binding of CaM to Trp3, -6, and -7 more effectively than that to Trp1, -2, -4, and -5. In inside-out membrane patches, Trp4 is activated strongly by calmidazolium, an antagonist of CaM, and a high (50 microm) but not a low (5 microm) concentration of the Trp-binding peptide of the IP(3)R. Our data support the view that both CaM and IP(3)Rs play important roles in controlling the gating of Trp-based channels. However, the sensitivity and responses to CaM and IP(3)Rs differ for each Trp.
PMID: 11290752External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
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
TRPC2 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Inference Prediction 11290752
TRPC2 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Inference Prediction 11290752
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R2 Inference Prediction 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Inference Prediction 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Inference Prediction 11290752
TRPC5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Inference Prediction 11290752
TRPC5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Inference Prediction 11290752
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Inference Prediction 11290752
TRPC7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Inference Prediction 11290752
TRPC7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Inference Prediction 11290752
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Mouse 688-974 In vitro translation Not specified Not specified Not specified 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 688-974 In vitro translation Human 669-698 E. coli 11290752
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Characterization Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Binding region mapping Stoichiometry Affinity (Kd) Reference
TRP channel Interactor
TRP channel Interactor Method Species Region Species Region
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Human 719-751 Not specified Not determined 11290752
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Human 720-749 Not specified Not determined 30 nM 11290752
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Human 719-751 Human 669-698 11290752
TRPC2 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Mouse 901-936 Not specified Not determined 11290752
TRPC2 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Mouse 905-934 Not specified Not determined 10 nM 11290752
TRPC2 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 901-936 Human 669-698 11290752
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Human 761-795 Not specified Not determined 11290752
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Human 764-793 Not specified Not determined 100 nM 11290752
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R1 Fusion protein-pull down assay Mouse 725-848 Not specified 654-688 11290752
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R2 Fusion protein-pull down assay Mouse 725-848 Not specified 675-695 11290752
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Human 761-795 Human 669-698 11290752
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 725-848 Human 681-698 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Mouse 789-812 Not specified Not determined 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Mouse 695-724 Not specified Not determined 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Mouse 695-724 Not specified Not determined 200 nM 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Mouse 787-812 Not specified Not determined 600 nM 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 781-864 Human 669-698 11290752
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 695-724 Human 669-698 11290752
TRPC5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Mouse 701-733 Not specified Not determined 11290752
TRPC5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Mouse 702-731 Not specified Not determined 220 nM 11290752
TRPC5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 701-733 Human 669-698 11290752
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Mouse 838-872 Not specified Not determined 11290752
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Mouse 843-872 Not specified Not determined 290 nM 11290752
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 838-872 Human 669-698 11290752
TRPC7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fusion protein-pull down assay Mouse 766-798 Not specified Not determined 11290752
TRPC7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calmodulin Fluorescence probe labeling Mouse 769-798 Not specified Not determined 19 nM 11290752
TRPC7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Fusion protein-pull down assay Mouse 766-798 Human 669-698 11290752
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

To prevent spam comments, we use reCAPTCHA. Please type correct words into the following box.