Cell Reports
Volume 18, Issue 11, 14 March 2017, Pages 2702-2714
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Article
γ-Protocadherins Interact with Neuroligin-1 and Negatively Regulate Dendritic Spine Morphogenesis

https://doi.org/10.1016/j.celrep.2017.02.060Get rights and content
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Highlights

  • γ-Protocadherins (γ-Pcdhs) regulate dendritic spine morphogenesis in the cerebral cortex

  • γ-Pcdhs interact with neuroligin-1 (Nlg1) and inhibit its interaction with neurexin1β

  • γ-Pcdhs inhibit Nlg1’s ability to induce presynaptic differentiation in vitro

  • γ-Pcdhs inhibit Nlg1’s ability to increase dendritic spine density in vitro

Summary

The 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules are critical for the elaboration of complex dendritic arbors in the cerebral cortex. Here, we provide evidence that the γ-Pcdhs negatively regulate synapse development by inhibiting the postsynaptic cell adhesion molecule, neuroligin-1 (Nlg1). Mice lacking all γ-Pcdhs in the forebrain exhibit significantly increased dendritic spine density in vivo, while spine density is significantly decreased in mice overexpressing one of the 22 γ-Pcdh isoforms. Co-expression of γ-Pcdhs inhibits the ability of Nlg1 to increase spine density and to induce presynaptic differentiation in hippocampal neurons in vitro. The γ-Pcdhs physically interact in cis with Nlg1 both in vitro and in vivo, and we present evidence that this disrupts Nlg1 binding to its presynaptic partner neurexin1β. Together with prior work, these data identify a mechanism through which γ-Pcdhs could coordinate dendrite arbor growth and complexity with spine maturation in the developing brain.

Keywords

synapse formation
synaptogenesis
synapse maturation
cell adhesion
spine morphology
spine maturation
neurexin
Pcdh
Protocadherin
Protocadherins

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