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Polycystin-L is a calcium-regulated cation channel permeable to calcium ions

Nature volume 401, pages 383–386 (1999)Cite this article

Abstract

Polycystic kidney diseases are genetic disorders in which the renal parenchyma is progressively replaced by fluid-filled cysts1. Two members of the polycystin family (polycystin-1 and -2) are mutated in autosomal dominant polycystic kidney disease (ADPKD)2,3,4,5, and polycystin-L is deleted in mice with renal and retinal defects6. Polycystins are membrane proteins that share significant sequence homology6,7, especially polycystin-2 and -L (50% identity and 71% similarity). The functions of the polycystins remain unknown. Here we show that polycystin-L is a calcium-modulated nonselective cation channel that is permeable to sodium, potassium and calcium ions. Patch-clamp experiments revealed single-channel activity with a unitary conductance of 137 pS. Channel activity was substantially increased when either the extracellular or intracellular calcium-ion concentration was raised, indicating that polycystin-L may act as a transducer of calcium-mediated signalling in vivo. Its large single-channel conductance and regulation by calcium ions distinguish it from other structurally related cation channels.

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Figure 1: PCL channel conductance in the resting state.
Figure 2: Polycystin-L conductance is stimulated by Ca2+.
Figure 3: Activity of PCL single channels is increased by Ca2+.
Figure 4: Effects of EGTA, divalent cations and protons.

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Acknowledgements

We thank P. Fong for providing pTLN2. X.-Z.C. is a recipient of the International Human Frontier Science Program Long-Term Fellowship. This work is supported by NARSAD and the Stanley Foundation (P.M.V.), the St. Giles Foundation (E.M.B.) and NIH (S.T.R., E.M.B., M.A.H. and J.Z.).

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Author notes

  1. Xing-Zhen Chen, Peter M. Vassilev and Edward M. Brown: These authors contributed equally to this work

Authors and Affiliations

  1. Renal and ,

    Xing-Zhen Chen, Nuria Basora, Ji-Bin Peng, Hideki Nomura, Yoav Segal, Stephen T. Reeders, Matthias A. Hediger & Jing Zhou

  2. Endocrine-Hypertension Divisions and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, 02115, Massachusetts, USA

    Peter M. Vassilev & Edward M. Brown

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Correspondence to Matthias A. Hediger or Jing Zhou.

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Chen, XZ., Vassilev, P., Basora, N. et al. Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. Nature 401, 383–386 (1999). https://doi.org/10.1038/43907

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