page 435) find that instead of anchoring cells to the outside matrix, dystroglycans in the nervous system bind to the membrane proteins neurexins, and therefore may help connect cells to each other.
Neurexins are a family of cell-surface proteins specific to neurons. Three genes encode neurexins, but rampant alternative splicing creates hundreds, if not thousands, of forms of the proteins. In a sample of 100 neurons, each neuron could have a different set of neurexins. The authors speculated that these diverse cell-surface proteins may regulate the formation of connections within the brain.
The study describes the search for the natural binding partners of neurexins. The black widow spider toxin is one known ligand for neurexins. The authors showed that the toxin competes with dystroglycan for binding to neurexins. Multiple other lines of evidence imply that in the brain dystroglycan and neurexin are connected. The connection may be regulated by alternative splicing, which can change the surfaces of repeated domains in neurexin, thereby affecting dystroglycan binding.
The asymmetric bond between these two types of cell-surface proteins could play an important part in the organization of synapses. The study also has implications for muscular dystrophy, which is often associated with cognitive defects. Although the relevant proteins have not yet been localized to synapses, it is possible that a dystrophin deficiency could destabilize dystroglycan–neurexin links and thus disturb connections between neurons in the brain. ▪