Structural evidence of adhesion process in axon guidance

​There is another auxiliary guidance cue, Draxin that can bind both DCC and Netrin-1 to play a regulatory role for Netrin-1. We have determined structures of Draxin in complex with DCC’s N-terminal horseshoe-like four Ig-like domains and also of a small conserved 22-residue sequence segment of Draxin, Draxin-22 in complex with Netrin-1. These two structures allow us to propose a model with DCC-Draxin-Netrin-1-DCC to form a bridge like arrangement to link two apposing axons. In other words, in addition to signaling, netrin can also mediate trans-adhesion between apposing cells decorated with its receptors DCC on the condition that the auxiliary guidance cue draxin is present. The adhesion-like arrangement fits recent haptotaxis model of axon guidance proposed in neuroscience community.
 
The above works have been a collaboration with scientists in EMBL and Peking University.