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PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans

Author

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  • Darshini Jeyasimman

    (Lee Kong Chian School of Medicine, Nanyang Technological University)

  • Bilge Ercan

    (Lee Kong Chian School of Medicine, Nanyang Technological University)

  • Dennis Dharmawan

    (Lee Kong Chian School of Medicine, Nanyang Technological University)

  • Tomoki Naito

    (Lee Kong Chian School of Medicine, Nanyang Technological University)

  • Jingbo Sun

    (Lee Kong Chian School of Medicine, Nanyang Technological University)

  • Yasunori Saheki

    (Lee Kong Chian School of Medicine, Nanyang Technological University
    Kumamoto University)

Abstract

Different types of cellular membranes have unique lipid compositions that are important for their functional identity. PI(4,5)P2 is enriched in the plasma membrane where it contributes to local activation of key cellular events, including actomyosin contraction and cytokinesis. However, how cells prevent PI(4,5)P2 from accumulating in intracellular membrane compartments, despite constant intermixing and exchange of lipid membranes, is poorly understood. Using the C. elegans early embryo as our model system, we show that the evolutionarily conserved lipid transfer proteins, PDZD-8 and TEX-2, act together with the PI(4,5)P2 phosphatases, OCRL-1 and UNC-26/synaptojanin, to prevent the build-up of PI(4,5)P2 on endosomal membranes. In the absence of these four proteins, large amounts of PI(4,5)P2 accumulate on endosomes, leading to embryonic lethality due to ectopic recruitment of proteins involved in actomyosin contractility. PDZD-8 localizes to the endoplasmic reticulum and regulates endosomal PI(4,5)P2 levels via its lipid harboring SMP domain. Accumulation of PI(4,5)P2 on endosomes is accompanied by impairment of their degradative capacity. Thus, cells use multiple redundant systems to maintain endosomal PI(4,5)P2 homeostasis.

Suggested Citation

  • Darshini Jeyasimman & Bilge Ercan & Dennis Dharmawan & Tomoki Naito & Jingbo Sun & Yasunori Saheki, 2021. "PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26177-z
    DOI: 10.1038/s41467-021-26177-z
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