title: Functional dependence of neuroligin on a new non-PDZ intracellular domain.
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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Seth L
authors.initials: SL
authors.lastname: Shipman
authors.forename: Eric
authors.initials: E
authors.lastname: Schnell
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hirai
authors.forename: Bo-Shiun
authors.initials: BS
authors.lastname: Chen
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Roche
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000235:genetics*; D005071:Evoked Potentials / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D035683:MicroRNAs; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D054731:PDZ Domains / Q000235:genetics*; D051381:Rats; D018091:Receptors, AMPA
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C093438:neuroligin 1; C098003:neuroligin 2; C098004:neuroligin 3