Functional dependence of neuroligin on a new non-PDZ intracellular domain

Seth L. Shipman, Eric Schnell, Takaaki Hirai, Bo Shiun Chen, Katherine W. Roche, Roger A. Nicoll

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Neuroligins, a family of postsynaptic adhesion molecules, are important in synaptogenesis through a well-characterized trans-synaptic interaction with neurexin. In addition, neuroligins are thought to drive postsynaptic assembly through binding of their intracellular domain to PSD-95. However, there is little direct evidence to support the functional necessity of the neuroligin intracellular domain in postsynaptic development. We found that presence of endogenous neuroligin obscured the study of exogenous mutated neuroligin. We therefore used chained microRNAs in rat organotypic hippocampal slices to generate a reduced background of endogenous neuroligin. On this reduced background, we found that neuroligin function was critically dependent on the cytoplasmic tail. However, this function required neither the PDZ ligand nor any other previously described cytoplasmic binding domain, but rather required a previously unknown conserved region. Mutation of a single critical residue in this region inhibited neuroligin-mediated excitatory synaptic potentiation. Finally, we found a functional distinction between neuroligins 1 and 3.

Original languageEnglish (US)
Pages (from-to)718-726
Number of pages9
JournalNature Neuroscience
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2011

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Functional dependence of neuroligin on a new non-PDZ intracellular domain'. Together they form a unique fingerprint.

  • Cite this

    Shipman, S. L., Schnell, E., Hirai, T., Chen, B. S., Roche, K. W., & Nicoll, R. A. (2011). Functional dependence of neuroligin on a new non-PDZ intracellular domain. Nature Neuroscience, 14(6), 718-726. https://doi.org/10.1038/nn.2825