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Phosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration

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  • Naoki Hisamoto

    (Nagoya University, Chikusa-ku)

  • Anna Tsuge

    (Nagoya University, Chikusa-ku)

  • Strahil Iv. Pastuhov

    (Nagoya University, Chikusa-ku)

  • Tatsuhiro Shimizu

    (Nagoya University, Chikusa-ku)

  • Hiroshi Hanafusa

    (Nagoya University, Chikusa-ku)

  • Kunihiro Matsumoto

    (Nagoya University, Chikusa-ku)

Abstract

Following axon injury, a cascade of signaling events is triggered to initiate axon regeneration. However, the mechanisms regulating axon regeneration are not well understood at present. In Caenorhabditis elegans, axon regeneration utilizes many of the components involved in phagocytosis, including integrin and Rac GTPase. Here, we identify the transthyretin (TTR)-like protein TTR-11 as a component functioning in axon regeneration upstream of integrin. We show that TTR-11 binds to both the extracellular domain of integrin-α and phosphatidylserine (PS). Axon injury induces the accumulation of PS around the injured axons in a manner dependent on TTR-11, the ABC transporter CED-7, and the caspase CED-3. Furthermore, we demonstrate that CED-3 activates CED-7 during axon regeneration. Thus, TTR-11 functions to link the PS injury signal to activation of the integrin pathway, which then initiates axon regeneration.

Suggested Citation

  • Naoki Hisamoto & Anna Tsuge & Strahil Iv. Pastuhov & Tatsuhiro Shimizu & Hiroshi Hanafusa & Kunihiro Matsumoto, 2018. "Phosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05478-w
    DOI: 10.1038/s41467-018-05478-w
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