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PI(3,5)P2 controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome

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  • Xian-ping Dong

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

  • Dongbiao Shen

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

  • Xiang Wang

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

  • Taylor Dawson

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

  • Xinran Li

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

  • Qi Zhang

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

  • Xiping Cheng

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

  • Yanling Zhang

    (University of Michigan)

  • Lois S. Weisman

    (University of Michigan)

  • Markus Delling

    (Children's Hospital Boston)

  • Haoxing Xu

    (Cellular, and Developmental Biology, University of Michigan, 3089 National Science Building (Kraus), 830 North University)

Abstract

Membrane fusion and fission events in intracellular trafficking are controlled by both intraluminal Ca2+ release and phosphoinositide (PIP) signalling. However, the molecular identities of the Ca2+ release channels and the target proteins of PIPs are elusive. In this paper, by direct patch-clamping of the endolysosomal membrane, we report that PI(3,5)P2, an endolysosome-specific PIP, binds and activates endolysosome-localized mucolipin transient receptor potential (TRPML) channels with specificity and potency. Both PI(3,5)P2-deficient cells and cells that lack TRPML1 exhibited enlarged endolysosomes/vacuoles and trafficking defects in the late endocytic pathway. We find that the enlarged vacuole phenotype observed in PI(3,5)P2-deficient mouse fibroblasts is suppressed by overexpression of TRPML1. Notably, this PI(3,5)P2-dependent regulation of TRPML1 is evolutionarily conserved. In budding yeast, hyperosmotic stress induces Ca2+ release from the vacuole. In this study, we show that this release requires both PI(3,5)P2 production and a yeast functional TRPML homologue. We propose that TRPMLs regulate membrane trafficking by transducing information regarding PI(3,5)P2 levels into changes in juxtaorganellar Ca2+, thereby triggering membrane fusion/fission events.

Suggested Citation

  • Xian-ping Dong & Dongbiao Shen & Xiang Wang & Taylor Dawson & Xinran Li & Qi Zhang & Xiping Cheng & Yanling Zhang & Lois S. Weisman & Markus Delling & Haoxing Xu, 2010. "PI(3,5)P2 controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome," Nature Communications, Nature, vol. 1(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:1:y:2010:i:1:d:10.1038_ncomms1037
    DOI: 10.1038/ncomms1037
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    Cited by:

    1. Kodaji Ha & Nadine Mundt-Machado & Paola Bisignano & Aide Pinedo & David R. Raleigh & Gabriel Loeb & Jeremy F. Reiter & Erhu Cao & Markus Delling, 2024. "Cilia-enriched oxysterol 7β,27-DHC is required for polycystin ion channel activation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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