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PMID:17541406

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Citation

Pilo Boyl, P, Di Nardo, A, Mulle, C, Sassoè-Pognetto, M, Panzanelli, P, Mele, A, Kneussel, M, Costantini, V, Perlas, E, Massimi, M, Vara, H, Giustetto, M and Witke, W (2007) Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior. EMBO J. 26:2991-3002

Abstract

Profilins are actin binding proteins essential for regulating cytoskeletal dynamics, however, their function in the mammalian nervous system is unknown. Here, we provide evidence that in mouse brain profilin1 and profilin2 have distinct roles in regulating synaptic actin polymerization with profilin2 preferring a WAVE-complex-mediated pathway. Mice lacking profilin2 show a block in synaptic actin polymerization in response to depolarization, which is accompanied by increased synaptic excitability of glutamatergic neurons due to higher vesicle exocytosis. These alterations in neurotransmitter release correlate with a hyperactivation of the striatum and enhanced novelty-seeking behavior in profilin2 mutant mice. Our results highlight a novel, profilin2-dependent pathway, regulating synaptic physiology, neuronal excitability, and complex behavior.

Links

PubMed PMC1894775 Online version:10.1038/sj.emboj.7601737

Keywords

Animals; Behavior, Animal/physiology; Exocytosis/physiology; Learning; Long-Term Potentiation; Memory; Mice; Neurons/physiology; Profilins/physiology

Significance

Annotations

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

MOUSE:PROF2

acts_upstream_of_or_within

GO:0030838: positive regulation of actin filament polymerization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3715145

P

Seeded From UniProt

complete

MOUSE:PROF2

acts_upstream_of_or_within

GO:2000300: regulation of synaptic vesicle exocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3715145

P

Seeded From UniProt

complete

MOUSE:PROF2

part_of

GO:0098794: postsynapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PROF2

involved_in

GO:2000300: regulation of synaptic vesicle exocytosis

ECO:0001225: knockout evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PROF2

involved_in

GO:2000300: regulation of synaptic vesicle exocytosis

ECO:0006013: patch-clamp recording evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PROF2

part_of

GO:0098685: Schaffer collateral - CA1 synapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PROF2

part_of

GO:0098978: glutamatergic synapse

ECO:0001225: knockout evidence used in manual assertion

C

  • part_of:(UBERON:0002435)

Seeded From UniProt

complete

MOUSE:PROF2

part_of

GO:0098978: glutamatergic synapse

ECO:0006013: patch-clamp recording evidence used in manual assertion

C

  • part_of:(UBERON:0002435)

Seeded From UniProt

complete

MOUSE:PROF2

part_of

GO:0098793: presynapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DYN1

part_of

GO:0043195: terminal bouton

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16894)

Seeded From UniProt

complete


See also

References

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