A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases

Peineau, Stéphane; Nicolas, Céline S.; Bortolotto, Zuner A.; Bhat, Ratan V.; Ryves, W. J.; Harwood, Adrian J.; Dournaud, Pascal; Fitzjohn, Stephen M.; Collingridge, Graham L.

doi:10.1186/1756-6606-2-22

Cited by 88 publications

(83 citation statements)

References 58 publications

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“…However, LTD does not require phosphorylation of Ago2 at S387, which is in agreement with a previous study demonstrating that LTD is normal in hippocampal slices from LIMK1 knockout mice (Meng et al , 2002). Furthermore, a previous report suggested that Akt activity is not required for the expression of CA3‐CA1 LTD (Peineau et al , 2009), which is consistent with our observation that Ago2 S387 mutants have no effect on CA3‐CA1 LTD.…”

Section: Discussionsupporting

confidence: 93%

NMDAR ‐dependent Argonaute 2 phosphorylation regulates mi RNA activity and dendritic spine plasticity

et al. 2018

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MicroRNAs (miRNAs) repress translation of target mRNAs by associating with Argonaute (Ago) proteins to form the RNA‐induced silencing complex (RISC), underpinning a powerful mechanism for fine‐tuning protein expression. Specific miRNAs are required for NMDA receptor (NMDAR)‐dependent synaptic plasticity by modulating the translation of proteins involved in dendritic spine morphogenesis or synaptic transmission. However, it is unknown how NMDAR stimulation stimulates RISC activity to rapidly repress translation of synaptic proteins. We show that NMDAR stimulation transiently increases Akt‐dependent phosphorylation of Ago2 at S387, which causes an increase in binding to GW182 and a rapid increase in translational repression of LIMK1 via miR‐134. Furthermore, NMDAR‐dependent down‐regulation of endogenous LIMK1 translation in dendrites and dendritic spine shrinkage requires phospho‐regulation of Ago2 at S387. AMPAR trafficking and hippocampal LTD do not involve S387 phosphorylation, defining this mechanism as a specific pathway for structural plasticity. This work defines a novel mechanism for the rapid transduction of NMDAR stimulation into miRNA‐mediated translational repression to control dendritic spine morphology.

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Section: Discussionsupporting

confidence: 93%

NMDAR ‐dependent Argonaute 2 phosphorylation regulates mi RNA activity and dendritic spine plasticity

et al. 2018

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“…Some, but not all, reports showed that inhibitors of p38 block LTD induction in the CA1, suggesting that GRF1 activation of p38 could be involved in this process as well (2,(25)(26)(27). However, stimuli that activate LTD did not lead to p38 activation (data not shown).…”

Section: Discussionmentioning

confidence: 73%

Domain Contributions to Signaling Specificity Differences Between Ras-Guanine Nucleotide Releasing Factor (Ras-GRF) 1 and Ras-GRF2

Jin

Bartolome

Arai

et al. 2014

Journal of Biological Chemistry

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Background: Ras-GRF1 and Ras-GRF2 are similar exchange factors with different functions in synaptic plasticity. Results: Chimeras between Ras-GRF proteins reveal that IQ, pleckstrin homology, coiled-coil, and CDC25 domains are most important for signaling specificity. Conclusion: Signaling specificity of GRF proteins is encoded in a surprisingly small number of their common domains. Significance: Domains of Ras-GRF proteins have been identified for future studies on signaling specificity.

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“…Indeed, PKA activation leads to the phosphorylation and activation of the cAMP response element binding protein (CREB), which is required for activity-dependent gene transcription during the late phase of postsynaptic LTP and controls neuronal excitability (for a review, see [45]), two mechanisms which could also contribute to the behavioural deficits observed in Ophn1-deficient mice. In addition, PKA signalling is involved in hippocampal LTD [46,47]. However, because dihydroxyphenylglycine (DHPG)-induced LTD is normal in Ophn1 2/y mice [9], it is unlikely that a deficit in hippocampal NMDAR-dependent LTD plays a major role in the impairment of contextual fear memory.…”

Section: Discussionmentioning

confidence: 99%

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

Khelfaoui

Gambino

Houbaert

et al. 2014

Phil. Trans. R. Soc. B

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Loss-of-function mutations in the gene encoding for the RhoGAP protein of oligophrenin-1 (OPHN1) lead to cognitive disabilities (CDs) in humans, yet the underlying mechanisms are not known. Here, we show that in mice constitutive lack of Ophn1 is associated with dysregulation of the cyclic adenosine monophosphate/phosphate kinase A (cAMP/PKA) signalling pathway in a brain-area-specific manner. Consistent with a key role of cAMP/PKA signalling in regulating presynaptic function and plasticity, we found that PKA-dependent presynaptic plasticity was completely abolished in affected brain regions, including hippocampus and amygdala. At the behavioural level, lack of OPHN1 resulted in hippocampus- and amygdala-related learning disabilities which could be fully rescued by the ROCK/PKA kinase inhibitor fasudil. Together, our data identify OPHN1 as a key regulator of presynaptic function and suggest that, in addition to reported postsynaptic deficits, loss of presynaptic plasticity contributes to the pathophysiology of CDs.

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A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases

Cited by 88 publications

References 58 publications

NMDAR ‐dependent Argonaute 2 phosphorylation regulates mi RNA activity and dendritic spine plasticity

NMDAR ‐dependent Argonaute 2 phosphorylation regulates mi RNA activity and dendritic spine plasticity

Domain Contributions to Signaling Specificity Differences Between Ras-Guanine Nucleotide Releasing Factor (Ras-GRF) 1 and Ras-GRF2

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

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