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Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes

Author

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  • Taketoshi Kajimoto

    (Kobe University Graduate School of Medicine, 7-5-1 Kusunoki, Kobe 650-0017, Japan)

  • Taro Okada

    (Kobe University Graduate School of Medicine, 7-5-1 Kusunoki, Kobe 650-0017, Japan)

  • Satoshi Miya

    (Kobe University Graduate School of Medicine, 7-5-1 Kusunoki, Kobe 650-0017, Japan)

  • Lifang Zhang

    (Kobe University Graduate School of Medicine, 7-5-1 Kusunoki, Kobe 650-0017, Japan)

  • Shun-ichi Nakamura

    (Kobe University Graduate School of Medicine, 7-5-1 Kusunoki, Kobe 650-0017, Japan)

Abstract

During late endosome maturation, cargo molecules are sorted into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs), and are either delivered to lysosomes for degradation or fused with the plasma membranes for exosome release. The mechanism underlying formation of exosomal ILVs and cargo sorting into ILVs destined for exosome release is still unclear. Here we show that inhibitory G protein (Gi)-coupled sphingosine 1-phosphate (S1P) receptors regulate exosomal MVE maturation. Gi-coupled S1P receptors on MVEs are constitutively activated through a constant supply of S1P via autocrine activation within organelles. We also found that the continuous activation of Gi-coupled S1P receptors on MVEs is essential for cargo sorting into ILVs destined for exosome release. Our results reveal a mechanism underlying ESCRT-independent maturation of exosomal MVEs.

Suggested Citation

  • Taketoshi Kajimoto & Taro Okada & Satoshi Miya & Lifang Zhang & Shun-ichi Nakamura, 2013. "Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes," Nature Communications, Nature, vol. 4(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3712
    DOI: 10.1038/ncomms3712
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    Cited by:

    1. Cheng Fu & Nan Yang & Jen-Zen Chuang & Nobuyuki Nakajima & Satoshi Iraha & Neeta Roy & Zhenquan Wu & Zhichun Jiang & Wataru Otsu & Roxana A. Radu & Howard Hua Yang & Maxwell Ping Lee & Tilla S. Worgal, 2024. "Mutant mice with rod-specific VPS35 deletion exhibit retinal α-synuclein pathology-associated degeneration," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Sarah Renaud & Anthony Lefebvre & Olivier Moralès & Nadira Delhem, 2019. "Mini Review - Exosomes from Discovery to Isolation," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 15(2), pages 11286-11293, February.

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