The intellectual disability protein PAK3 regulates oligodendrocyte precursor cell differentiation

Neurobiology of Disease
Majistor Raj Luxman Maglorius RenkilarajLamia Bouslama-Oueghlani

Abstract

Oligodendrocyte and myelin deficits have been reported in mental/psychiatric diseases. The p21-activated kinase 3 (PAK3), a serine/threonine kinase, whose activity is stimulated by the binding of active Rac and Cdc42 GTPases is affected in these pathologies. Indeed, many mutations of Pak3 gene have been described in non-syndromic intellectual disability diseases. Pak3 is expressed mainly in the brain where its role has been investigated in neurons but not in glial cells. Here, we showed that PAK3 is highly expressed in oligodendrocyte precursors (OPCs) and its expression decreases in mature oligodendrocytes. In the developing white matter of the Pak3 knockout mice, we found defects of oligodendrocyte differentiation in the corpus callosum and to a lesser extent in the anterior commissure, which were compensated at the adult stage. In vitro experiments in OPC cultures, derived from Pak3 knockout and wild type brains, support a developmental and cell-autonomous role for PAK3 in regulating OPC differentiation into mature oligodendrocytes. Moreover, we did not detect any obvious alterations of the proliferation or migration of Pak3 null OPCs compared to wild type. Overall, our data highlight PAK3 as a new regulator of OPC different...Continue Reading

References

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Aug 9, 2005·Developmental Biology·Lamia Bouslama-OueghlaniIsabelle Dusart
Jul 18, 2012·Nature·Youngjin LeeJeffrey D Rothstein
Feb 18, 2014·International Review of Cell and Molecular Biology·Helen KingClaire M Wells

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Citations

Mar 3, 2020·Frontiers in Cellular Neuroscience·Giorgia FattoriniFiorenzo Conti
Mar 9, 2019·Neurochemical Research·Tanya L Brown, Wendy B Macklin
Jan 17, 2020·Human Molecular Genetics·Charlotte CastillonRoseline Poirier
Oct 27, 2020·The Journal of International Medical Research·Yi ZhengWei Zhong
May 21, 2020·Cell Reports·Martha S WindremSteven A Goldman
Jul 3, 2021·International Journal of Molecular Sciences·Carla LiaciGiorgio R Merlo

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