title: Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina.
abstract: Neuroligins (NL1-NL4) are postsynaptic adhesion proteins that control the maturation and function of synapses in the central nervous system (CNS). Loss-of-function mutations in NL4 are linked to rare forms of monogenic heritable autism, but its localization and function are unknown. Using the retina as a model system, we show that NL4 is preferentially localized to glycinergic postsynapses and that the loss of NL4 is accompanied by a reduced number of glycine receptors mediating fast glycinergic transmission. Accordingly, NL4-deficient ganglion cells exhibit slower glycinergic miniature postsynaptic currents and subtle alterations in their stimulus-coding efficacy, and inhibition within the NL4-deficient retinal network is altered as assessed by electroretinogram recordings. These data indicate that NL4 shapes network activity and information processing in the retina by modulating glycinergic inhibition. Importantly, NL4 is also targeted to inhibitory synapses in other areas of the CNS, such as the thalamus, colliculi, brainstem, and spinal cord, and forms complexes with the inhibitory postsynapse proteins gephyrin and collybistin in vivo, indicating that NL4 is an important component of glycinergic postsynapses.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Hoon
authors.forename: Tolga
authors.initials: T
authors.lastname: Soykan
authors.forename: Björn
authors.initials: B
authors.lastname: Falkenburger
authors.forename: Matthieu
authors.initials: M
authors.lastname: Hammer
authors.forename: Annarita
authors.initials: A
authors.lastname: Patrizi
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Schmidt
authors.forename: Marco
authors.initials: M
authors.lastname: Sassoè-Pognetto
authors.forename: Siegrid
authors.initials: S
authors.lastname: Löwel
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
authors.forename: Holger
authors.initials: H
authors.lastname: Taschenberger
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Frédérique
authors.initials: F
authors.lastname: Varoqueaux
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D004596:Electroretinography; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000378:metabolism*; D012160:Retina / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; C527118:Nlgn4 protein, mouse; D018009:Receptors, Glycine