A necessary step toward complete functional recovery after spinal cord injury is the regeneration of axons. Axon regrowth after injury is prevented by a myriad of intrinsic and extrinsic factors. In this issue of The EMBO Journal, Huang et al (2016) demonstrate that the cell adhesion molecule NB‐3 (CNTN6) functions as a major brake on axon regrowth when it is activated by NB‐3 from scar‐forming cells at the injury site. Disruption of this NB‐3 trans‐cellular signaling led to impressive axon regrowth after spinal cord transection.
See also: Z Huang et al (August 2016)
NB‐3 is a member of the contactin subfamily within the immunoglobulin superfamily (IgSF) of cell adhesion molecules (CAMs). IgSF CAMs regulate axon growth, branching, and synapse formation and plasticity in the developing and mature nervous system (Leshchyns'ka & Sytnyk, 2016). Members of the contactin subfamily interact with proteins of the L1cam IgSF subfamily, and both families play essential functions in neuronal network formation in the developing nervous system (Kamiguchi et al, 1998; Wei & Ryu, 2012).
IgSF CAMs are involved in intricate webs of signaling (Fig 1A). They can form interactions in cis with other molecules in the same membrane or in trans with molecules on adjacent cells. These interactions can also be with the same CAM (homophilic) or with different molecules (heterophilic) (Maness & Schachner, 2007). As receptors, they can transduce signals via a variety of intracellular partners (Herron et al, 2009) that often result in cytoskeletal remodeling (Leshchyns'ka & Sytnyk, 2016). Thus, IgSF CAMs represent promising targets to trigger axon regeneration following CNS injury. …