The specific α-neurexin interactor calsyntenin-3 promotes excitatory and inhibitory synapse development.
| Autor: | Pettem KL; Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 2B5, Canada., Yokomaku D, Luo L, Linhoff MW, Prasad T, Connor SA, Siddiqui TJ, Kawabe H, Chen F, Zhang L, Rudenko G, Wang YT, Brose N, Craig AM |
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| Jazyk: | angličtina |
| Zdroj: | Neuron [Neuron] 2013 Oct 02; Vol. 80 (1), pp. 113-28. Date of Electronic Publication: 2013 Oct 02. |
| DOI: | 10.1016/j.neuron.2013.07.016 |
| Abstrakt: | 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. (Copyright © 2013 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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