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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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    1. Gilbert Di Paolo & Pietro De Camilli, 2006. "Phosphoinositides in cell regulation and membrane dynamics," Nature, Nature, vol. 443(7112), pages 651-657, October.
    2. Joachim Moser von Filseck & Stefano Vanni & Bruno Mesmin & Bruno Antonny & Guillaume Drin, 2015. "A phosphatidylinositol-4-phosphate powered exchange mechanism to create a lipid gradient between membranes," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    3. Michiko Shirane & Mariko Wada & Keiko Morita & Nahoki Hayashi & Reina Kunimatsu & Yuki Matsumoto & Fumiko Matsuzaki & Hirokazu Nakatsumi & Keisuke Ohta & Yasushi Tamura & Keiichi I. Nakayama, 2020. "Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    4. Yael Elbaz-Alon & Yuting Guo & Nadav Segev & Michal Harel & Daniel E. Quinnell & Tamar Geiger & Ori Avinoam & Dong Li & Jodi Nunnari, 2020. "PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    5. Curtis M. Schauder & Xudong Wu & Yasunori Saheki & Pradeep Narayanaswamy & Federico Torta & Markus R. Wenk & Pietro De Camilli & Karin M. Reinisch, 2014. "Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer," Nature, Nature, vol. 510(7506), pages 552-555, June.
    6. ., 2017. "Western extended economic development," Chapters, in: A General Theory of Economic Development, chapter 4, pages 63-73, Edward Elgar Publishing.
    7. Jiangqing Dong & Ximing Du & Huan Wang & Jue Wang & Chang Lu & Xiang Chen & Zhiwen Zhu & Zhipu Luo & Li Yu & Andrew J. Brown & Hongyuan Yang & Jia-Wei Wu, 2019. "Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    8. Laura L. E. Cowen & Panagiotis Besbeas & Byron J. T. Morgan & Carl J. Schwarz, 2017. "Hidden Markov models for extended batch data," Biometrics, The International Biometric Society, vol. 73(4), pages 1321-1331, December.
    9. Joost C.M. Holthuis & Anant K. Menon, 2014. "Lipid landscapes and pipelines in membrane homeostasis," Nature, Nature, vol. 510(7503), pages 48-57, June.
    Full references (including those not matched with items on IDEAS)

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