| Autor: |
Steffen DM; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA.; Department of Biology, The University of Iowa, Iowa City, IA, 52242, USA., Ferri SL; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA.; Department of Neuroscience and Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA., Marcucci CG; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA.; Department of Biology, The University of Iowa, Iowa City, IA, 52242, USA., Blocklinger KL; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA.; Department of Neuroscience and Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA., Molumby MJ; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA.; Department of Biology, The University of Iowa, Iowa City, IA, 52242, USA., Abel T; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA.; Department of Neuroscience and Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA., Weiner JA; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA. joshua-weiner@uiowa.edu.; Department of Biology, The University of Iowa, Iowa City, IA, 52242, USA. joshua-weiner@uiowa.edu. |
| Abstrakt: |
Cell adhesion molecules (CAMs) are key players in the formation of neural circuits during development. The γ-protocadherins (γ-Pcdhs), a family of 22 CAMs encoded by the Pcdhg gene cluster, are known to play important roles in dendrite arborization, axon targeting, and synapse development. We showed previously that multiple γ-Pcdhs interact physically with the autism-associated CAM neuroligin-1, and inhibit the latter's ability to promote excitatory synapse maturation. Here, we show that γ-Pcdhs can also interact physically with the related neuroligin-2, and inhibit this CAM's ability to promote inhibitory synapse development. In an artificial synapse assay, γ-Pcdhs co-expressed with neuroligin-2 in non-neuronal cells reduce inhibitory presynaptic maturation in contacting hippocampal axons. Mice lacking the γ-Pcdhs from the forebrain (including the cortex, the hippocampus, and portions of the amygdala) exhibit increased inhibitory synapse density and increased co-localization of neuroligin-2 with inhibitory postsynaptic markers in vivo. These Pcdhg mutants also exhibit defective social affiliation and an anxiety-like phenotype in behavioral assays. Together, these results suggest that γ-Pcdhs negatively regulate neuroligins to limit synapse density in a manner that is important for normal behavior. |
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