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PMID:20962234

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Citation

Oh, D, Han, S, Seo, J, Lee, JR, Choi, J, Groffen, J, Kim, K, Cho, YS, Choi, HS, Shin, H, Woo, J, Won, H, Park, SK, Kim, SY, Jo, J, Whitcomb, DJ, Cho, K, Kim, H, Bae, YC, Heisterkamp, N, Choi, SY and Kim, E (2010) Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins. J. Neurosci. 30:14134-44

Abstract

Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer's disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-positive chronic myelogenous leukemia. Despite the fact that BCR mRNAs are abundantly expressed in the brain, the neural functions of BCR protein have remained obscure. We report here that BCR and its close relative active BCR-related (ABR) localize at excitatory synapses and directly interact with PSD-95, an abundant postsynaptic scaffolding protein. Mice deficient for BCR or ABR show enhanced basal Rac1 activity but only a small increase in spine density. Importantly, mice lacking BCR or ABR exhibit a marked decrease in the maintenance, but not induction, of long-term potentiation, and show impaired spatial and object recognition memory. These results suggest that BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions.

Links

PubMed PMC5076888 Online version:10.1523/JNEUROSCI.1711-10.2010

Keywords

Animals; Biolistics; Cells, Cultured; Dendritic Spines/metabolism; Electrophysiology; GTPase-Activating Proteins/biosynthesis; GTPase-Activating Proteins/genetics; Hippocampus/cytology; Hippocampus/metabolism; Immunohistochemistry; Learning/physiology; Long-Term Potentiation/physiology; Male; Maze Learning/physiology; Memory/physiology; Mice; Mice, Knockout; Microscopy, Electron; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/physiology; Rats; Rats, Sprague-Dawley; Recognition (Psychology)/physiology; Synaptic Transmission/physiology; Transfection; rac1 GTP-Binding Protein/biosynthesis; rac1 GTP-Binding Protein/genetics

Significance

Annotations

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

RAT:ABR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31016

F

Seeded From UniProt

complete

RAT:ABR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0005589: confocal microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:ABR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:ABR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:ABR

is_active_in

GO:0099092: postsynaptic density, intracellular component

ECO:0005589: confocal microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:ABR

is_active_in

GO:0099092: postsynaptic density, intracellular component

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:ABR

is_active_in

GO:0099092: postsynaptic density, intracellular component

ECO:0006042: cell fractionation evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:BCR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31016

F

Seeded From UniProt

complete

RAT:BCR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0000279: qualitative western immunoblotting evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:BCR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:BCR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0006042: cell fractionation evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:BCR

is_active_in

GO:0099092: postsynaptic density, intracellular component

ECO:0000279: qualitative western immunoblotting evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:BCR

is_active_in

GO:0099092: postsynaptic density, intracellular component

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:BCR

is_active_in

GO:0099092: postsynaptic density, intracellular component

ECO:0006042: cell fractionation evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BCR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P78352

F

Seeded From UniProt

complete

RAT:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:A0A0G2JTR4
UniProtKB:F1LXF1

F

Seeded From UniProt

complete

HUMAN:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11274
UniProtKB:Q12979

F

Seeded From UniProt

complete

HUMAN:ABR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P78352

F

Seeded From UniProt

complete

MOUSE:ABR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ABR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ABR

is_active_in

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0001225: knockout evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ABR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0001225: knockout evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:BCR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCR

is_active_in

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0001225: knockout evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BCR

is_active_in

GO:0098978: glutamatergic synapse

ECO:0001225: knockout evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:BCR

part_of

GO:0098978: glutamatergic synapse

ECO:0001225: knockout evidence used in manual assertion

C

part_of:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:BCR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

  • occurs_in:(GO:0098978)
  • occurs_in:(UBERON:0000061)
  • occurs_in:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:BCR

part_of

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0001225: knockout evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BCR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ABR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ABR

involved_in

GO:0050804: modulation of chemical synaptic transmission

ECO:0001225: knockout evidence used in manual assertion

P

  • occurs_in:(GO:0098978)
  • occurs_in:(UBERON:0000061)
  • occurs_in:(UBERON:0002421)

Seeded From UniProt

complete

MOUSE:ABR

part_of

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0001225: knockout evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ABR

part_of

GO:0098978: glutamatergic synapse

ECO:0001225: knockout evidence used in manual assertion

C

part_of:(UBERON:0002421)

Seeded From UniProt

complete

Notes

See also

References

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