ArticleThe Journal of biological chemistry2011
p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its interaction with the Nck2/Grb4 protein adaptor.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
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- Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
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- NCK1 Modulates Neuronal Actin Dynamics and Promotes Dendritic Spine, Synapse, and Memory Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The molecular basis of p21-activated kinase-associated neurodevelopmental disorders: From genotype to phenotype.Frontiers in neuroscience · 2023Review
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- PAK3 is a key signature gene of the glioma proneural subtype and affects its proliferation, differentiation and growth.Cellular oncology (Dordrecht, Netherlands) · 2021Article
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- Nck adaptors at a glance.Journal of cell science · 2021Article
- The cross-talk of energy sensing and mitochondrial anchoring sustains synaptic efficacy by maintaining presynaptic metabolism.Nature metabolism · 2020Article
- Nck1, But Not Nck2, Mediates Disturbed Flow-Induced p21-Activated Kinase Activation and Endothelial Permeability.Journal of the American Heart Association · 2020Article
- Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function.Cell reports · 2018Article
- Next-Generation Sequencing Reveals Novel Mutations in X-linked Intellectual Disability.Omics : a journal of integrative biology · 2017Article
- Identification of a Protein Network Driving Neuritogenesis of MGE-Derived GABAergic Interneurons.Frontiers in cellular neuroscience · 2016Article
- Roles of Rac1 and Rac3 GTPases during the development of cortical and hippocampal GABAergic interneurons.Frontiers in cellular neuroscience · 2014Review
- Group I p21-activated kinases facilitate Tax-mediated transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats.Retrovirology · 2013Article
- Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics.Nature communications · 2013Article
- The p21-activated kinase PAK3 forms heterodimers with PAK1 in brain implementing trans-regulation of PAK3 activity.The Journal of biological chemistry · 2012Article
- PAK in Alzheimer disease, Huntington disease and X-linked mental retardation.Cellular logistics · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the p21-activated kinase 3 gene (pak3) are responsible for nonsyndromic forms of mental retardation. Expression of mutated PAK3 proteins in hippocampal neurons induces abnormal dendritic spine morphology and long term potentiation anomalies, whereas pak3 gene invalidation leads to cognitive impairments. How PAK3 regulates synaptic plasticity is still largely unknown. To better understand how PAK3 affects neuronal synaptic plasticity, we focused on its interaction with the Nck adaptors that play a crucial role in PAK signaling. We report here that PAK3 interacts preferentially with Nck2/Grb4 in brain extracts and in transfected cells. This interaction is independent of PAK3 kinase activity. Selective uncoupling of the Nck2 interactions in acute cortical slices using an interfering peptide leads to a rapid increase in evoked transmission to pyramidal neurons. The P12A mutation in the PAK3 protein strongly decreases the interaction with Nck2 but only slightly with Nck1. In transfected hippocampal cultures, expression of the P12A-mutated protein has no effect on spine morphogenesis or synaptic density. The PAK3-P12A mutant does not affect synaptic transmission, whereas the expression of the wild-type PAK3 protein decreases the amplitude of spontaneous miniature excitatory currents. Altogether, these data show that PAK3 down-regulates synaptic transmission through its interaction with Nck2.
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