RRC ID 54293
Author Hisamoto N, Tsuge A, Pastuhov SI, Shimizu T, Hanafusa H, Matsumoto K.
Title Phosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration.
Journal Nat Commun
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.
Volume 9(1)
Pages 3099
Published 2018-8-6
DOI 10.1038/s41467-018-05478-w
PII 10.1038/s41467-018-05478-w
PMID 30082731
PMC PMC6079064
MeSH 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
IF 12.121
Times Cited 6
Resource
C.elegans tm6877