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PMID:19996097

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Citation

Tada, H, Okano, HJ, Takagi, H, Shibata, S, Yao, I, Matsumoto, M, Saiga, T, Nakayama, KI, Kashima, H, Takahashi, T, Setou, M and Okano, H (2010) Fbxo45, a novel ubiquitin ligase, regulates synaptic activity. J. Biol. Chem. 285:3840-9

Abstract

Neurons communicate with each other through synapses. To establish the precise yet flexible connections that make up neural networks in the brain, continuous synaptic modulation is required. The ubiquitin-proteasome system of protein degradation is one of the critical mechanisms that underlie this process, playing crucial roles in the regulation of synaptic structure and function. We identified a novel ubiquitin ligase, Fbxo45, that functions at synapses. Fbxo45 is evolutionarily conserved and selectively expressed in the nervous system. We demonstrated that the knockdown of Fbxo45 in primary cultured hippocampal neurons resulted in a greater frequency of miniature excitatory postsynaptic currents. We also found that Fbxo45 induces the degradation of a synaptic vesicle-priming factor, Munc13-1. We propose that Fbxo45 plays an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse.

Links

PubMed PMC2823526 Online version:10.1074/jbc.M109.046284

Keywords

Amino Acid Sequence; Animals; Brain/cytology; Brain/metabolism; Brain/physiology; COS Cells; Cell Line; Cells, Cultured; Cercopithecus aethiops; Excitatory Postsynaptic Potentials; F-Box Proteins/genetics; F-Box Proteins/metabolism; Gene Expression Profiling; Humans; Immunoblotting; In Situ Hybridization; Mice; Microscopy, Immunoelectron; Molecular Sequence Data; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/metabolism; Neurons/physiology; Neurons/ultrastructure; Protein Binding; RNA Interference; S-Phase Kinase-Associated Proteins/genetics; S-Phase Kinase-Associated Proteins/metabolism; Sequence Homology, Amino Acid; Synapses/metabolism; Synapses/physiology; Synaptic Transmission/genetics; Synaptic Transmission/physiology; Ubiquitination

Significance

Annotations

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

HUMAN:SKP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K3B1

F

Seeded From UniProt

complete

MOUSE:UN13A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8K3B1

F

Seeded From UniProt

complete

MOUSE:FBSP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q4KUS2

F

Seeded From UniProt

complete

MOUSE:FBSP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P63208

F

Seeded From UniProt

complete

MOUSE:FBSP1

located_in

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBSP1

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBSP1

involved_in

GO:0016567: protein ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FBSP1

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0098978: glutamatergic synapse

ECO:0005589: confocal microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0098978: glutamatergic synapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0098793: presynapse

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0098793: presynapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0099523: presynaptic cytosol

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0099523: presynaptic cytosol

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0099524: postsynaptic cytosol

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBSP1

part_of

GO:0099524: postsynaptic cytosol

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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