title: Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin.
abstract: In the mammalian CNS, each neuron typically receives thousands of synaptic inputs from diverse classes of neurons. Synaptic transmission to the postsynaptic neuron relies on localized and transmitter-specific differentiation of the plasma membrane with postsynaptic receptor, scaffolding, and adhesion proteins accumulating in precise apposition to presynaptic sites of transmitter release. We identified protein interactions of the synaptic adhesion molecule neuroligin 2 that drive postsynaptic differentiation at inhibitory synapses. Neuroligin 2 binds the scaffolding protein gephyrin through a conserved cytoplasmic motif and functions as a specific activator of collybistin, thus guiding membrane tethering of the inhibitory postsynaptic scaffold. Complexes of neuroligin 2, gephyrin and collybistin are sufficient for cell-autonomous clustering of inhibitory neurotransmitter receptors. Deletion of neuroligin 2 in mice perturbs GABAergic and glycinergic synaptic transmission and leads to a loss of postsynaptic specializations specifically at perisomatic inhibitory synapses.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Poulopoulos
authors.forename: Gayane
authors.initials: G
authors.lastname: Aramuni
authors.forename: Guido
authors.initials: G
authors.lastname: Meyer
authors.forename: Tolga
authors.initials: T
authors.lastname: Soykan
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Hoon
authors.forename: Theofilos
authors.initials: T
authors.lastname: Papadopoulos
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhang
authors.forename: Ingo
authors.initials: I
authors.lastname: Paarmann
authors.forename: Céline
authors.initials: C
authors.lastname: Fuchs
authors.forename: Kirsten
authors.initials: K
authors.lastname: Harvey
authors.forename: Peter
authors.initials: P
authors.lastname: Jedlicka
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Schwarzacher
authors.forename: Heinrich
authors.initials: H
authors.lastname: Betz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Harvey
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Frédérique
authors.initials: F
authors.lastname: Varoqueaux
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C577403:Arhgef9 protein, mouse; C577404:Arhgef9 protein, rat; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D064067:Rho Guanine Nucleotide Exchange Factors; C073441:gephyrin; C098003:neuroligin 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine