p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its interaction with the Nck2/Grb4 protein adaptor.

The Journal of Biological Chemistry
Emmanuel ThévenotJean-Vianney Barnier

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 decre...Continue Reading

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Citations

Nov 30, 2013·Nature Communications·Lisa BuvallPeter Mundel
Jul 21, 2012·The Journal of Biological Chemistry·Gaëlle CombeauJean-Vianney Barnier
Sep 2, 2014·Journal of Physiology, Paris·André P KothDaniela M Barros
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May 10, 2017·Omics : a Journal of Integrative Biology·Babylakshmi MuthusamyHarsha Gowda
Jan 3, 2014·Physiological Reviews·Carlo Sala, Menahem Segal
May 30, 2020·Journal of the American Heart Association·Mabruka AlfaidiA Wayne Orr
Jan 10, 2017·Frontiers in Cellular Neuroscience·Sira A FranchiIvan de Curtis

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