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

Nat Commun. 2018 Aug 6;9(1):3099. doi: 10.1038/s41467-018-05478-w.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Axons / metabolism
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Caspases / metabolism
  • Cytoskeletal Proteins / metabolism
  • Integrins / metabolism
  • Lipids / chemistry
  • Mutation
  • Nerve Regeneration
  • Phagocytosis
  • Phosphatidylserines / metabolism*
  • Plasmids / metabolism
  • Signal Transduction*
  • rac GTP-Binding Proteins / metabolism


  • ATP-Binding Cassette Transporters
  • CED-7 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • Ina-1 protein, C elegans
  • Integrins
  • Lipids
  • Phosphatidylserines
  • Caspases
  • ced-3 protein, C elegans
  • rac GTP-Binding Proteins