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PMID:17541406
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 |
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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 |
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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 |
|
Seeded From UniProt |
complete | |
MOUSE:PROF2 |
part_of |
GO:0098978: glutamatergic synapse |
ECO:0006013: patch-clamp recording evidence used in manual assertion |
C |
|
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 |
|
Seeded From UniProt |
complete | |
See also
References
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