Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Cbln1 (a.k.a. precerebellin) is a unique bidirectional synaptic organizer that plays an essential role in the formation and maintenance of excitatory synapses between granule cells and Purkinje cells in the mouse cerebellum. Cbln1 secreted from cerebellar granule cells directly induces presynaptic differentiation and indirectly serves as a postsynaptic organizer by binding to its receptor, the δ2 glutamate receptor. However, it remains unclear how Cbln1 binds to the presynaptic sites and interacts with other synaptic organizers. Furthermore, although Cbln1 and its family members Cbln2 and Cbln4 are expressed in brain regions other than the cerebellum, it is unknown whether they regulate synapse formation in these brain regions. In this study, we showed that Cbln1 and Cbln2, but not Cbln4, specifically bound to its presynaptic receptor -α and β isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] - and induced synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. Cbln1 competed with synaptogenesis mediated by neuroligin 1, which lacks the splice sites A and B, but not leucine-rich repeat transmembrane protein 2, possibly by sharing the presynaptic receptor NRXs(S4+). However, unlike neurexins/neuroligins or neurexins/leucine-rich repeat transmembrane proteins, the interaction between NRX1β(S4+) and Cbln1 was insensitive to extracellular Ca2+ concentrations. These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions.

Original languageEnglish
Pages (from-to)1447-1461
Number of pages15
JournalEuropean Journal of Neuroscience
Volume33
Issue number8
DOIs
Publication statusPublished - 2011 Apr

Fingerprint

Synapses
Cerebellum
Presynaptic Receptors
Brain
Maintenance
Proteins
Purkinje Cells
Glutamate Receptors
Protein Isoforms
Neurons
leucine-rich repeat proteins
neuroligin 1
In Vitro Techniques

Keywords

  • Cerebellum
  • Hippocampus
  • Leucine-rich repeat transmembrane protein
  • Mouse
  • Neurexin
  • Neuroligin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{d11be83a38b6468ca3cf9e140444ade9,
title = "Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions",
abstract = "Cbln1 (a.k.a. precerebellin) is a unique bidirectional synaptic organizer that plays an essential role in the formation and maintenance of excitatory synapses between granule cells and Purkinje cells in the mouse cerebellum. Cbln1 secreted from cerebellar granule cells directly induces presynaptic differentiation and indirectly serves as a postsynaptic organizer by binding to its receptor, the δ2 glutamate receptor. However, it remains unclear how Cbln1 binds to the presynaptic sites and interacts with other synaptic organizers. Furthermore, although Cbln1 and its family members Cbln2 and Cbln4 are expressed in brain regions other than the cerebellum, it is unknown whether they regulate synapse formation in these brain regions. In this study, we showed that Cbln1 and Cbln2, but not Cbln4, specifically bound to its presynaptic receptor -α and β isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] - and induced synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. Cbln1 competed with synaptogenesis mediated by neuroligin 1, which lacks the splice sites A and B, but not leucine-rich repeat transmembrane protein 2, possibly by sharing the presynaptic receptor NRXs(S4+). However, unlike neurexins/neuroligins or neurexins/leucine-rich repeat transmembrane proteins, the interaction between NRX1β(S4+) and Cbln1 was insensitive to extracellular Ca2+ concentrations. These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions.",
keywords = "Cerebellum, Hippocampus, Leucine-rich repeat transmembrane protein, Mouse, Neurexin, Neuroligin",
author = "Keiko Matsuda and Michisuke Yuzaki",
year = "2011",
month = "4",
doi = "10.1111/j.1460-9568.2011.07638.x",
language = "English",
volume = "33",
pages = "1447--1461",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions

AU - Matsuda, Keiko

AU - Yuzaki, Michisuke

PY - 2011/4

Y1 - 2011/4

N2 - Cbln1 (a.k.a. precerebellin) is a unique bidirectional synaptic organizer that plays an essential role in the formation and maintenance of excitatory synapses between granule cells and Purkinje cells in the mouse cerebellum. Cbln1 secreted from cerebellar granule cells directly induces presynaptic differentiation and indirectly serves as a postsynaptic organizer by binding to its receptor, the δ2 glutamate receptor. However, it remains unclear how Cbln1 binds to the presynaptic sites and interacts with other synaptic organizers. Furthermore, although Cbln1 and its family members Cbln2 and Cbln4 are expressed in brain regions other than the cerebellum, it is unknown whether they regulate synapse formation in these brain regions. In this study, we showed that Cbln1 and Cbln2, but not Cbln4, specifically bound to its presynaptic receptor -α and β isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] - and induced synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. Cbln1 competed with synaptogenesis mediated by neuroligin 1, which lacks the splice sites A and B, but not leucine-rich repeat transmembrane protein 2, possibly by sharing the presynaptic receptor NRXs(S4+). However, unlike neurexins/neuroligins or neurexins/leucine-rich repeat transmembrane proteins, the interaction between NRX1β(S4+) and Cbln1 was insensitive to extracellular Ca2+ concentrations. These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions.

AB - Cbln1 (a.k.a. precerebellin) is a unique bidirectional synaptic organizer that plays an essential role in the formation and maintenance of excitatory synapses between granule cells and Purkinje cells in the mouse cerebellum. Cbln1 secreted from cerebellar granule cells directly induces presynaptic differentiation and indirectly serves as a postsynaptic organizer by binding to its receptor, the δ2 glutamate receptor. However, it remains unclear how Cbln1 binds to the presynaptic sites and interacts with other synaptic organizers. Furthermore, although Cbln1 and its family members Cbln2 and Cbln4 are expressed in brain regions other than the cerebellum, it is unknown whether they regulate synapse formation in these brain regions. In this study, we showed that Cbln1 and Cbln2, but not Cbln4, specifically bound to its presynaptic receptor -α and β isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] - and induced synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. Cbln1 competed with synaptogenesis mediated by neuroligin 1, which lacks the splice sites A and B, but not leucine-rich repeat transmembrane protein 2, possibly by sharing the presynaptic receptor NRXs(S4+). However, unlike neurexins/neuroligins or neurexins/leucine-rich repeat transmembrane proteins, the interaction between NRX1β(S4+) and Cbln1 was insensitive to extracellular Ca2+ concentrations. These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions.

KW - Cerebellum

KW - Hippocampus

KW - Leucine-rich repeat transmembrane protein

KW - Mouse

KW - Neurexin

KW - Neuroligin

UR - http://www.scopus.com/inward/record.url?scp=79954486224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954486224&partnerID=8YFLogxK

U2 - 10.1111/j.1460-9568.2011.07638.x

DO - 10.1111/j.1460-9568.2011.07638.x

M3 - Article

C2 - 21410790

AN - SCOPUS:79954486224

VL - 33

SP - 1447

EP - 1461

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 8

ER -