The neurons do not spend their whole time crossing and recrossing the midline of the fly because the midline repellent Slit binds the Robo receptor. Now, Dickson and colleagues show that crossing events require that the guidance protein Comm grab onto Robo in the Golgi and send it on a suicide journey to late endosomes and lysosomes. This eliminates the influence of Slit, allowing neurons to cross. After crossing, Comm is rapidly turned off to reestablish Robo signaling and prevent recrossing.
In the few cases studied, Comm transcription turns on just as neurons initiate their turn toward the midline. This is probably controlled by cell fate determinants that, in turn, are determined by the time and place that the neuron is born. The shutting down of Comm, post-crossing, may be controlled by either a midline-derived signal or a timing mechanism.
Comm's activity relies only on a minimal sorting motif, so there may well be Comm-like proteins in mammals. Furthermore, the existence of multiple Comm proteins suggest that these proteins may take many different victims to their deaths. “I guarantee you Comm is doing a lot more than sorting Robo receptors,” says Dickson. ▪