Little is known about the molecules mediating the cross‐talk between post‐traumatic axons and scar‐forming cells after spinal cord injury. We found that a sustained NB‐3 induction was simultaneously present in the terminations of post‐traumatic corticospinal axons and scar‐forming cells at the spinal lesion site, where they were in direct contact when axons tried to penetrate the glial scar. The regrowth of corticospinal axons was enhanced in vivo with NB‐3 deficiency or interruption of NB‐3 trans‐homophilic interactions. Biochemical, in vitro and in vivo evidence demonstrated that NB‐3 homophilically interacted in trans to initiate a growth inhibitory signal transduction from scar‐forming cells to neurons by modulating mTOR activity via CHL1 and PTPσ. NB‐3 deficiency promoted BMS scores, electrophysiological transmission, and synapse reformation between regenerative axons and neurons. Our findings demonstrate that NB‐3 trans‐homophilic interactions mediate the cross‐talk between post‐traumatic axons and scar‐forming cells and impair the intrinsic growth ability of injured axons.
NB‐3 trans‐homophilic interactions mediate the molecular cross‐talk between post‐traumatic axons and scar‐forming cells and impair the intrinsic growth ability of injured axons by modulating mTOR activity via CHL1 and PTPσ.
SCI‐induced NB‐3 in injured axons and scar‐forming cells interacts homophilically.
Interruption of NB‐3 homophilic binding enhances regrowth of corticospinal axons.
Trans‐homophilic interactions of NB‐3 downregulate mTOR signaling via CHL1 and PTPσ.
- Received November 11, 2015.
- Revision received March 20, 2016.
- Accepted April 12, 2016.
- © 2016 The Authors