title: Glutamate receptor δ1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with neurexins through cerebellin precursor protein subtypes.
abstract: Glutamate receptor (GluR) δ1 is widely expressed in the developing forebrain, whereas GluRδ2 is selectively expressed in cerebellar Purkinje cells. Recently, we found that trans-synaptic interaction of postsynaptic GluRδ2 and pre-synaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates excitatory synapse formation in the cerebellum. Thus, a question arises whether GluRδ1 regulates synapse formation in the forebrain. In this study, we showed that the N-terminal domain of GluRδ1 induced inhibitory presynaptic differentiation of some populations of cultured cortical neurons. When Cbln1 or Cbln2 was added to cultures, GluRδ1 expressed in HEK293T cells induced preferentially inhibitory presynaptic differentiation of cultured cortical neurons. The synaptogenic activity of GluRδ1 was suppressed by the addition of the extracellular domain of NRXN1α or NRXN1β containing splice segment 4. Cbln subtypes directly bound to the N-terminal domain of GluRδ1. The synaptogenic activity of GluRδ1 in the presence of Cbln subtypes correlated well with their binding affinities. When transfected to cortical neurons, GluRδ1 stimulated inhibitory synapse formation in the presence of Cbln1 or Cbln2. These results together with differential interactions of Cbln subtypes with NRXN variants suggest that GluRδ1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with NRXNs containing splice segment 4 through Cbln subtypes.
authors.affiliation: Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Yasumura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uemura
authors.forename: Jae-Yeol
authors.initials: JY
authors.lastname: Joo
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques; D018274:Electroporation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020349:Surface Plasmon Resonance; D013569:Synapses / Q000378:metabolism*
chemical_list: C092370:Cbln1 protein, mouse; C558312:Cbln2 protein, mouse; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017470:Receptors, Glutamate; C108929:glutamate receptor delta 1