DOI: 10.1073/pnas.051632698. Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain

Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain

10.1073/pnas.051632698

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Mammalian homologues of Drosophila Trp form plasma membrane channels that mediate Ca 2+ influx in response to activation of phospholipase C and internal Ca 2+ store depletion. Previous studies showed that human Trp3 is activated by inositol 1,4,5-trisphosphate (IP 3 ) receptors (IP 3 Rs) and identified interacting domains, one on Trp and two on IP 3 R. We now find that Trp3 binds Ca 2+ -calmodulin (Ca 2+ /CaM) at a site that overlaps with the IP 3 R binding domain. Using patch-clamp recordings from inside-out patches, we further show that Trp3 has a high intrinsic activity that is suppressed by Ca 2+ /CaM under resting conditions, and that Trp3 is activated by the following: a Trp-binding peptide from IP 3 R that displaces CaM from Trp3, a myosin light chain kinase Ca 2+ /CaM binding peptide that prevents CaM from binding to Trp3, and calmidazolium, an inactivator of Ca 2+ /CaM. We conclude that inhibition of the inhibitory action of CaM is a key step of Trp3 channel activation by IP 3 Rs.

Bibliography

Zhang, Z., Tang, J., Tikunova, S., Johnson, J. D., Chen, Z., Qin, N., Dietrich, A., Stefani, E., Birnbaumer, L., & Zhu, M. X. (2001). Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain. Proceedings of the National Academy of Sciences, 98(6), 3168â3173.

Authors 10

Zongming Zhang (first)
Jisen Tang (additional)
Svetlana Tikunova (additional)
J. David Johnson (additional)
Zhangguo Chen (additional)
Ning Qin (additional)
Alexander Dietrich (additional)
Enrico Stefani (additional)
Lutz Birnbaumer (additional)
Michael Xi Zhu (additional)

References 45 Referenced 199

Dates

Type	When
Created	23 years ago (July 26, 2002, 10:41 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 3:20 p.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 12:17 p.m.)
Issued	24 years, 5 months ago (Feb. 27, 2001)
Published	24 years, 5 months ago (Feb. 27, 2001)
Published Online	24 years, 5 months ago (Feb. 27, 2001)
Published Print	24 years, 5 months ago (March 13, 2001)

Funders 0

None

BibTeX

@article{Zhang_2001, title={Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.051632698}, DOI={10.1073/pnas.051632698}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Zhang, Zongming and Tang, Jisen and Tikunova, Svetlana and Johnson, J. David and Chen, Zhangguo and Qin, Ning and Dietrich, Alexander and Stefani, Enrico and Birnbaumer, Lutz and Zhu, Michael Xi}, year={2001}, month=feb, pages={3168–3173} }

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  "abstract": "<jats:p>\n            Mammalian homologues of\n            <jats:italic>Drosophila</jats:italic>\n            Trp form plasma\n membrane channels that mediate Ca\n            <jats:sup>2+</jats:sup>\n            influx in response to\n activation of phospholipase C and internal Ca\n            <jats:sup>2+</jats:sup>\n            store\n depletion. Previous studies showed that human Trp3 is activated by\n inositol 1,4,5-trisphosphate (IP\n            <jats:sub>3</jats:sub>\n            ) receptors\n (IP\n            <jats:sub>3</jats:sub>\n            Rs) and identified interacting domains, one on Trp and\n two on IP\n            <jats:sub>3</jats:sub>\n            R. We now find that Trp3 binds\n Ca\n            <jats:sup>2+</jats:sup>\n            -calmodulin (Ca\n            <jats:sup>2+</jats:sup>\n            /CaM) at a\n site that overlaps with the IP\n            <jats:sub>3</jats:sub>\n            R binding domain. Using\n patch-clamp recordings from inside-out patches, we further show that\n Trp3 has a high intrinsic activity that is suppressed by\n Ca\n            <jats:sup>2+</jats:sup>\n            /CaM under resting conditions, and that Trp3 is\n activated by the following: a Trp-binding peptide from IP\n            <jats:sub>3</jats:sub>\n            R\n that displaces CaM from Trp3, a myosin light chain kinase\n Ca\n            <jats:sup>2+</jats:sup>\n            /CaM binding peptide that prevents CaM from binding\n to Trp3, and calmidazolium, an inactivator of Ca\n            <jats:sup>2+</jats:sup>\n            /CaM.\n We conclude that inhibition of the inhibitory action of CaM is a key\n step of Trp3 channel activation by IP\n            <jats:sub>3</jats:sub>\n            Rs.\n          </jats:p>",
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