γ-Neurexin and Frizzled Mediate Parallel Synapse Assembly Pathways Antagonized by Receptor Endocytosis

Peri T. Kurshan, Sean A. Merrill, Yongming Dong, Chen Ding, Marc Hammarlund, Jihong Bai, Erik M. Jorgensen, Kang Shen

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Synapse formation defines neuronal connectivity and is thus essential for neuronal circuit assembly. Trans-synaptic interactions of cell adhesion molecules are thought to induce synapse assembly. Here we demonstrate that a recently discovered and conserved short form of neurexin, γ-neurexin, which lacks canonical extracellular domains, is nonetheless sufficient to promote presynaptic assembly in the nematode C. elegans. γ- but not α-neurexin is required for assembling active zone components, recruiting synaptic vesicles, and clustering calcium channels at release sites to promote evoked synaptic transmission. Furthermore, we find that neurexin functions in parallel with the transmembrane receptor Frizzled, as the absence of both proteins leads to an enhanced phenotype—the loss of most synapses. Frizzled's pro-synaptogenic function is independent of its ligand, Wnt. Wnt binding instead eliminates synapses by inducing Frizzled's endocytosis and the downregulation of neurexin. These results reveal how pro- and anti-synaptogenic factors converge to precisely sculpt circuit formation in vivo. Kurshan et al. show that a short version of the cell-adhesion molecule neurexin that lacks canonical extracellular domains can nonetheless drive presynaptic assembly. It functions in parallel with the Wnt receptor Frizzled. Wnt eliminates synapses via Frizzled endocytosis and neurexin downregulation.

Original languageEnglish (US)
Pages (from-to)150-166.e4
JournalNeuron
Volume100
Issue number1
DOIs
StatePublished - Oct 10 2018

    Fingerprint

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kurshan, P. T., Merrill, S. A., Dong, Y., Ding, C., Hammarlund, M., Bai, J., Jorgensen, E. M., & Shen, K. (2018). γ-Neurexin and Frizzled Mediate Parallel Synapse Assembly Pathways Antagonized by Receptor Endocytosis. Neuron, 100(1), 150-166.e4. https://doi.org/10.1016/j.neuron.2018.09.007