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ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology

Author

Listed:
  • Anne-Laure Perraud

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Andrea Fleig

    (Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii)

  • Christopher A. Dunn

    (Johns Hopkins University)

  • Leigh Ann Bagley

    (Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii)

  • Pierre Launay

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Carsten Schmitz

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Alexander J. Stokes

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Qiqin Zhu

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Maurice J. Bessman

    (Johns Hopkins University)

  • Reinhold Penner

    (Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii)

  • Jean-Pierre Kinet

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Andrew M. Scharenberg

    (Beth Israel Deaconess Medical Center and Harvard Medical School
    University of Washington and Children's Hospital and Medical Center)

Abstract

Free ADP-ribose (ADPR), a product of NAD hydrolysis and a breakdown product of the calcium-release second messenger cyclic ADPR (cADPR), has no defined role as an intracellular signalling molecule in vertebrate systems. Here we show that a 350-amino-acid protein (designated NUDT9) and a homologous domain (NUDT9 homology domain) near the carboxy terminus of the LTRPC2/TrpC7 putative cation channel1 both function as specific ADPR pyrophosphatases. Whole-cell and single-channel analysis of HEK-293 cells expressing LTRPC2 show that LTRPC2 functions as a calcium-permeable cation channel that is specifically gated by free ADPR. The expression of native LTRPC2 transcripts is detectable in many tissues including the U937 monocyte cell line, in which ADPR induces large cation currents (designated IADPR) that closely match those mediated by recombinant LTRPC2. These results indicate that intracellular ADPR regulates calcium entry into cells that express LTRPC2.

Suggested Citation

  • Anne-Laure Perraud & Andrea Fleig & Christopher A. Dunn & Leigh Ann Bagley & Pierre Launay & Carsten Schmitz & Alexander J. Stokes & Qiqin Zhu & Maurice J. Bessman & Reinhold Penner & Jean-Pierre Kine, 2001. "ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology," Nature, Nature, vol. 411(6837), pages 595-599, May.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6837:d:10.1038_35079100
    DOI: 10.1038/35079100
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