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ORP5 and ORP8 bind phosphatidylinositol-4, 5-biphosphate (PtdIns(4,5)P 2) and regulate its level at the plasma membrane

Author

Listed:
  • Rajesh Ghai

    (The University of New South Wales
    The University of Queensland)

  • Ximing Du

    (The University of New South Wales)

  • Huan Wang

    (Tsinghua University)

  • Jiangqing Dong

    (Tsinghua University)

  • Charles Ferguson

    (The University of Queensland
    The University of Queensland)

  • Andrew J. Brown

    (The University of New South Wales)

  • Robert G. Parton

    (The University of Queensland
    The University of Queensland)

  • Jia-Wei Wu

    (Tsinghua University)

  • Hongyuan Yang

    (The University of New South Wales)

Abstract

ORP5 and ORP8, members of the oxysterol-binding protein (OSBP)-related proteins (ORP) family, are endoplasmic reticulum membrane proteins implicated in lipid trafficking. ORP5 and ORP8 are reported to localize to endoplasmic reticulum–plasma membrane junctions via binding to phosphatidylinositol-4-phosphate (PtdIns(4)P), and act as a PtdIns(4)P/phosphatidylserine counter exchanger between the endoplasmic reticulum and plasma membrane. Here we provide evidence that the pleckstrin homology domain of ORP5/8 via PtdIns(4,5)P 2, and not PtdIns(4)P binding mediates the recruitment of ORP5/8 to endoplasmic reticulum–plasma membrane contact sites. The OSBP-related domain of ORP8 can extract and transport multiple phosphoinositides in vitro, and knocking down both ORP5 and ORP8 in cells increases the plasma membrane level of PtdIns(4,5)P 2 with little effect on PtdIns(4)P. Overall, our data show, for the first time, that phosphoinositides other than PtdIns(4)P can also serve as co-exchangers for the transport of cargo lipids by ORPs.

Suggested Citation

  • Rajesh Ghai & Ximing Du & Huan Wang & Jiangqing Dong & Charles Ferguson & Andrew J. Brown & Robert G. Parton & Jia-Wei Wu & Hongyuan Yang, 2017. "ORP5 and ORP8 bind phosphatidylinositol-4, 5-biphosphate (PtdIns(4,5)P 2) and regulate its level at the plasma membrane," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00861-5
    DOI: 10.1038/s41467-017-00861-5
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    Cited by:

    1. Yunyun Wang & Zhenni Li & Xinyu Wang & Ziyuan Zhao & Li Jiao & Ruming Liu & Keying Wang & Rui Ma & Yang Yang & Guo Chen & Yong Wang & Xin Bian, 2023. "Insights into membrane association of the SMP domain of extended synaptotagmin," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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