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Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4.

Publication ,  Journal Article
Hu, H; Grandl, J; Bandell, M; Petrus, M; Patapoutian, A
Published in: Proc Natl Acad Sci U S A
February 3, 2009

Temperature-activated transient receptor potential ion channels (thermoTRPs) are polymodal detectors of various stimuli including temperature, voltage, and chemicals. To date, it is not known how TRP channels integrate the action of such disparate stimuli. Identifying specific residues required for channel-activation by distinct stimuli is necessary for understanding overall TRP channel function. TRPV3 is activated by warm temperatures and various chemicals, and is modulated by voltage. One potent activator of TRPV3 is 2-aminoethyl diphenylborinate (2-APB), a synthetic chemical that modulates many TRP channels. In a high-throughput mutagenesis screen of approximately 14,000 mutated mouse TRPV3 clones, we found 2 residues (H426 and R696) specifically required for sensitivity of TRPV3 to 2-APB, but not to camphor or voltage. The cytoplasmic N-terminal mutation H426N in human, dog, and frog TRPV3 also effectively abolished 2-APB activation without affecting camphor responses. Interestingly, chicken TRPV3 is weakly sensitive to 2-APB, and the equivalent residue at 426 is an asparagine (N). Mutating this residue to histidine induced 2-APB sensitivity of chicken TRPV3 to levels comparable for other TRPV3 orthologs. The cytoplasmic C-terminal mutation R696K in the TRP box displayed 2-APB specific deficits only in the presence of extracellular calcium, suggesting involvement in gating. TRPV4, a related thermoTRP, is 2-APB insensitive and has variant sequences at both residues identified here. Remarkably, mutating these 2 residues in TRPV4 to TRPV3 sequences (N426H and W737R) was sufficient to induce TRPV3-like 2-APB sensitivity. Therefore, 2-APB activation of TRPV3 is separable from other activation mechanisms, and depends on 2 cytoplasmic residues.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 3, 2009

Volume

106

Issue

5

Start / End Page

1626 / 1631

Location

United States

Related Subject Headings

  • Temperature
  • TRPV Cation Channels
  • Sequence Homology, Amino Acid
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Humans
  • DNA Primers
  • Cell Line
  • Calcium
  • Boron Compounds
 

Citation

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Hu, H., Grandl, J., Bandell, M., Petrus, M., & Patapoutian, A. (2009). Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4. Proc Natl Acad Sci U S A, 106(5), 1626–1631. https://doi.org/10.1073/pnas.0812209106
Hu, Hongzhen, Jörg Grandl, Michael Bandell, Matt Petrus, and Ardem Patapoutian. “Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4.Proc Natl Acad Sci U S A 106, no. 5 (February 3, 2009): 1626–31. https://doi.org/10.1073/pnas.0812209106.
Hu H, Grandl J, Bandell M, Petrus M, Patapoutian A. Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1626–31.
Hu, Hongzhen, et al. “Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4.Proc Natl Acad Sci U S A, vol. 106, no. 5, Feb. 2009, pp. 1626–31. Pubmed, doi:10.1073/pnas.0812209106.
Hu H, Grandl J, Bandell M, Petrus M, Patapoutian A. Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1626–1631.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 3, 2009

Volume

106

Issue

5

Start / End Page

1626 / 1631

Location

United States

Related Subject Headings

  • Temperature
  • TRPV Cation Channels
  • Sequence Homology, Amino Acid
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Humans
  • DNA Primers
  • Cell Line
  • Calcium
  • Boron Compounds