The Specific α-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development


Perturbations of cell surface synapse-organizing proteins, particularly α-neurexins, contribute to neurodevelopmental and psychiatric disorders. From an unbiased screen, we identify calsyntenin-3 (alcadein-β) as a synapse-organizing protein unique in binding and recruiting α-neurexins, but not β-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 α-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 α-neurexin-specific binding partner required for normal functional GABAergic and glutamatergic synapse development.

DOI: 10.1016/j.neuron.2013.07.016

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@article{Pettem2013TheS, title={The Specific α-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development}, author={Katherine L. Pettem and Daisaku Yokomaku and Lin Luo and Michael Linhoff and Tuhina Prasad and Steven A. Connor and Tabrez J. Siddiqui and Hiroshi Kawabe and Fang Chen and Ling Zhang and Gabby Rudenko and Yu Tian Wang and Nils Brose and Ann Marie Craig}, journal={Neuron}, year={2013}, volume={80}, pages={113-128} }