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PMID:21356198

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Citation

Joo, JY, Lee, SJ, Uemura, T, Yoshida, T, Yasumura, M, Watanabe, M and Mishina, M (2011) Differential interactions of cerebellin precursor protein (Cbln) subtypes and neurexin variants for synapse formation of cortical neurons. Biochem. Biophys. Res. Commun. 406:627-32

Abstract

Trans-synaptic interaction of postsynaptic glutamate receptor δ2 and presynaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates synapse formation in the cerebellum [T. Uemura, S.J. Lee, M. Yasumura, T. Takeuchi, T. Yoshida, M. Ra, R. Taguchi, K. Sakimura, M. Mishina, Cell 141 (2010) 1068-1079]. This finding raises a question whether other Cbln family members interact with NRXNs to regulate synapse formation in the forebrain. Here, we showed that Cbln1 and Cbln2 induced presynaptic differentiation of cultured cortical neurons, while Cbln4 exhibited little activity. When compared with neuroligin 1, Cbln1 and Cbln2 induced preferentially inhibitory presynaptic differentiation rather than excitatory one in cortical cultures. The synaptogenic activities of Cbln1 and Cbln2 were suppressed by the addition of the extracellular domain of NRXN1β to the cortical neuron cultures. Consistently, Cbln1 and Cbln2 showed robust binding activities to NRXN1α and three β-NRXNs, while only weak interactions were observed between Cbln4 and NRXNs. The interactions of Cbln1, Cbln2 and Cbln4 were selective for NRXN variants containing splice segment (S) 4. Affinities for NRXNs estimated by surface plasmon resonance analysis were variable among Cbln subtypes. Cbln1 showed higher affinities to NRXNs than Cbln2, while the binding ability of Cbln4 was much lower than those of Cbln1 and Cbln2. The affinities of Cbln1 and Cbln2 were comparable between NRXN1α and NRXN1β, but those for NRXN2β and NRXN3β were lower. These results suggest that Cbln subtypes exert synaptogenic activities in cortical neurons by differentially interacting with NRXN variants containing S4.

Links

PubMed Online version:10.1016/j.bbrc.2011.02.108

Keywords

Animals; Cerebral Cortex/cytology; Cerebral Cortex/physiology; Mice; Mice, Inbred ICR; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/cytology; Neurons/physiology; Protein Binding; Protein Precursors/genetics; Protein Precursors/metabolism; Synapses/metabolism; Synapses/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NRX2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BME9

F

Seeded From UniProt

complete

MOUSE:NRX2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BGU2
PR:Q9R171

F

Seeded From UniProt

complete

MOUSE:VIAAT

located_in

GO:0060077: inhibitory synapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000117)
  • part_of:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:BSN

located_in

GO:0048786: presynaptic active zone

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000117)
  • part_of:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:NRX1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BME9

F

Seeded From UniProt

complete

MOUSE:NRX1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BGU2
PR:Q9R171

F

Seeded From UniProt

complete

MOUSE:NRX1B

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88281
MGI:MGI:88282

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:VGLU1

located_in

GO:0060076: excitatory synapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000117)
  • part_of:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:CBLN2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:E9Q7X7
PR:Q9CS84

F

Seeded From UniProt

complete

MOUSE:CBLN2

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:CBLN4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:E9Q7X7
PR:Q9CS84

F

Seeded From UniProt

complete

MOUSE:NLGN1

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:NRX1A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BME9

F

Seeded From UniProt

complete

MOUSE:NRX1A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BGU2
PR:Q9R171

F

Seeded From UniProt

complete

MOUSE:NRX1A

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88281
MGI:MGI:88282

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:CBLN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:E9Q7X7
PR:Q9CS84

F

Seeded From UniProt

complete

MOUSE:CBLN1

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:CBLN1

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1096391

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:NLGN1

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(EMAPA:17544)
  • regulates_o_occurs_in:(CL:0000117)

Seeded From UniProt

complete

MOUSE:BSN

part_of

GO:0048786: presynaptic active zone

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17544)
  • part_of:(CL:0000117)

Seeded From UniProt

complete

MOUSE:VGLU1

part_of

GO:0060076: excitatory synapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17544)
  • part_of:(CL:0000117)

Seeded From UniProt

complete

MOUSE:NRX1B

acts_upstream_of_or_within

GO:0051965: positive regulation of synapse assembly

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88281
MGI:MGI:88282

P

  • regulates_o_occurs_in:(EMAPA:17544)
  • regulates_o_occurs_in:(CL:0000117)

Seeded From UniProt

complete


See also

References

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