title: Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation.
abstract: Differentiation of pre- and postsynaptic sites is coordinated by reciprocal interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC) synapses, dendritic spines are autonomously formed without PF influence. However, little is known about how presynaptic structural changes are induced and how they lead to differentiation of mature synapses. Here, we show that Cbln1 released from PFs induces dynamic structural changes in PFs by a mechanism that depends on postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx). Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed circular structures and encapsulated PC spines. Such structural changes in PFs were associated with the accumulation of synaptic vesicles and GluD2, leading to formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism.
authors.affiliation: Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ito-Ishida
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Eriko
authors.initials: E
authors.lastname: Miura
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
authors.forename: Shigeo
authors.initials: S
authors.lastname: Okabe
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C092370:Cbln1 protein, mouse; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; D011498:Protein Precursors; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2