Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain (original) (raw)

Nature volume 434, pages 99–104 (2005)Cite this article

Abstract

Many ion channels are regulated by lipids1,2,3, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cγ1 (PLC-γ1) binds to and regulates TRPC3 channels4, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-γ1 that includes a partial pleckstrin homology (PH) domain—a consensus lipid-binding and protein-binding sequence5,6. We have developed a gestalt algorithm to detect hitherto ‘invisible’ PH and PH-like domains, and now report that the partial PH domain of PLC-γ1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.

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Acknowledgements

We thank D. Boehning, G. Caraveo, J. Kendall, A. Resnick and R. E. Rothe for discussion; P.-G. Suh for the gift of the PLC-γ1 antibody; and B. VanRossum for graphics. This research was supported by US Public Health Service Grants and a Research Scientist Award (to S.H.S.), a National Institutes of Health Grant (to D.L.G.), and National Research Service Awards (to R.L.P.).

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Author notes

  1. Damian B. van Rossum and Randen L. Patterson: These authors contributed equally to this work

Authors and Affiliations

  1. Departments of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
    Damian B. van Rossum, Sumit Sharma, Roxanne K. Barrow, Michael Kornberg & Solomon H. Snyder
  2. Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
    Solomon H. Snyder
  3. Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
    Solomon H. Snyder
  4. Department of Biology, The Pennsylvania State University, State College, Pennsylvania, 16802, USA
    Randen L. Patterson
  5. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA
    Donald L. Gill

Authors

  1. Damian B. van Rossum
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  2. Randen L. Patterson
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  3. Sumit Sharma
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  4. Roxanne K. Barrow
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  5. Michael Kornberg
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  6. Donald L. Gill
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  7. Solomon H. Snyder
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Correspondence toSolomon H. Snyder.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figures 1-3

Complementation analyses identify PH domain code within TRPC3, smallwing, alpha 1 syntrophin, syngap and TRPV1. (PDF 447 kb)

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van Rossum, D., Patterson, R., Sharma, S. et al. Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain.Nature 434, 99–104 (2005). https://doi.org/10.1038/nature03340

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