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PubMed: 27796283

Title
The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines.
Journal
Nature communications
Volume
7
Issue
None
Pages
13282
Date
2016-10-31
Authors
Ip NY | Lai KO | Liang Z | Plattner F | Shen Y | Wong CC | Yates JR 3rd | Zhan Y

Evidence 1ed28a4963
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These findings suggest that CaMKv is required for both synaptic transmission and protein synthesis-dependent LTP in the hippocampus.

bp(MESH:"Long-Term Potentiation") association p(HGNC:CAMKV) View Subject | View Object

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Annotations
Uberon
hippocampal formation

p(HGNC:CAMKV) regulates bp(GO:"neuron-neuron synaptic transmission") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

p(HGNC:CAMKV) association bp(MESH:"Long-Term Potentiation") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

Evidence 91176ce88f
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Rac1 and RhoA are the best-studied members that regulate spine dynamics; their activation facilitates and prevents dendritic spine formation, respectively

a(MESH:"Dendritic Spines") positiveCorrelation bp(GO:"dendritic spine development") View Subject | View Object

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bp(GO:"dendritic spine development") positiveCorrelation a(MESH:"Dendritic Spines") View Subject | View Object

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act(p(HGNC:RHOA)) decreases bp(GO:"dendritic spine development") View Subject | View Object

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act(p(HGNC:RAC1)) increases bp(GO:"dendritic spine development") View Subject | View Object

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Evidence bcf11dce44
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In contrast, much less is known about how RhoA is regulated by excitatory glutamate receptors. The Rho-GEF Lfc (also known as GEF-H1) is one notable link between RhoA activity and glutamate receptors18. Lfc is inhibited by AMPA receptors; Lfc and RhoA inhibition is implicated in spine maintenance10. RhoA hyperactivity can lead to spine loss and impaired synaptic function.

a(MESH:"Dendritic Spines") negativeCorrelation act(p(HGNC:RHOA)) View Subject | View Object

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complex(GO:"AMPA glutamate receptor complex") decreases act(p(HGNC:ARHGEF2)) View Subject | View Object

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act(p(HGNC:RHOA)) negativeCorrelation a(MESH:"Dendritic Spines") View Subject | View Object

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act(p(HGNC:ARHGEF2)) regulates a(MESH:"Dendritic Spines") View Subject | View Object

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Evidence 1d634d03f2
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CaMKs functionally link NMDA (N-methyl-d-aspartate) receptors to Rac1 activation via the phosphorylation of specific guanine nucleotide exchange factors (GEFs) such as Kalirin-7, TIAM1 and β-PIX

a(MESH:"Receptors, N-Methyl-D-Aspartate") increases act(p(HGNC:RAC1)) View Subject | View Object

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a(MESH:"Receptors, N-Methyl-D-Aspartate") increases p(HGNC:TIAM1, pmod(Ph)) View Subject | View Object

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p(HBP:"Kalirin 7", pmod(Ph, Thr, 95)) increases act(p(HBP:"Kalirin 7")) View Subject | View Object

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act(p(HBP:"Kalirin 7")) increases act(p(HGNC:RAC1)) View Subject | View Object

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act(p(HGNC:ARHGEF7)) increases act(p(HGNC:RAC1)) View Subject | View Object

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p(HGNC:ARHGEF7, pmod(Ph, Ser, 516)) increases act(p(HGNC:ARHGEF7)) View Subject | View Object

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p(HGNC:CAMK1) increases p(HGNC:ARHGEF7, pmod(Ph, Ser, 516)) View Subject | View Object

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p(HGNC:CAMK2B) increases p(HBP:"Kalirin 7", pmod(Ph, Thr, 95)) View Subject | View Object

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p(HGNC:TIAM1, pmod(Ph)) increases act(p(HGNC:RAC1)) View Subject | View Object

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Evidence 150d3a42a1
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These observations suggest that CaMKv blocks RhoA activity by preventing its interaction with Lfc. These results demonstrate that CaMKv regulates spine maintenance through RhoA inhibition. The suppression of the Lfc/RhoA pathway by AMPA receptors is implicated in dendritic spine maintenance10. Given that CaMKv expression is upregulated by synaptic activity, CaMKv may be a key signalling protein that transduces the signals from AMPA receptors to suppress RhoA during activity-dependent spine maintenance. Corroborating this, the AMPA receptor blocker NBQX attenuated CaMKv expression in neurons (Fig. 3i,j). Importantly, CaMKv overexpression completely rescued NBQX-induced spine loss (Fig. 3k,l). These findings collectively reveal that activity-dependent CaMKv expression and the subsequent inhibition of Lfc/RhoA are required to mediate AMPA receptor function in spine maintenance.

act(a(MESH:Neurons)) increases p(HGNC:CAMKV) View Subject | View Object

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complex(p(HGNC:ARHGEF2), p(HGNC:RHOA)) positiveCorrelation act(p(HGNC:RHOA)) View Subject | View Object

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act(p(HGNC:RHOA)) positiveCorrelation complex(p(HGNC:ARHGEF2), p(HGNC:RHOA)) View Subject | View Object

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act(p(HGNC:CAMKV)) decreases complex(p(HGNC:ARHGEF2), p(HGNC:RHOA)) View Subject | View Object

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act(p(HGNC:CAMKV)) decreases act(p(HGNC:RHOA)) View Subject | View Object

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Evidence ef9f2ca5e2
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However, co-expression of the phospho-mimetic T345E failed to restore the defects in spine density after CaMKv depletion (Fig. 4l,m), suggesting that CaMKv phosphorylation by Cdk5 at Thr345 inhibits its function.

p(HGNC:CDK5) increases p(HGNC:CAMKV, pmod(Ph, Thr, 345)) View Subject | View Object

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p(HGNC:CAMKV, pmod(Ph, Thr, 345)) decreases act(p(HGNC:CAMKV)) View Subject | View Object

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.