文摘
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Summary
Perturbations of cell surface synapse-organizing proteins, particularly ¦Á-neurexins, contribute to neurodevelopmental and psychiatric disorders. From an?unbiased screen, we identify calsyntenin-3 (alcadein-¦Â) as a synapse-organizing protein unique in binding and recruiting ¦Á-neurexins, but not ¦Â-neurexins. Calsyntenin-3 is present in many pyramidal neurons throughout cortex and hippocampus but is most highly expressed in interneurons. The transmembrane form of calsyntenin-3 can trigger excitatory and inhibitory presynapse differentiation in contacting axons. However, calsyntenin-3-shed ectodomain, which represents about half the calsyntenin-3 pool in brain, suppresses the ability of multiple ¦Á-neurexin partners including neuroligin 2 and LRRTM2 to induce presynapse differentiation. Clstn3?/? mice show reductions in excitatory and inhibitory synapse density by confocal and electron microscopy and corresponding deficits in synaptic transmission. These results identify calsyntenin-3 as an ¦Á-neurexin-specific binding partner required for normal functional GABAergic and glutamatergic synapse development.
