Distinct, but compensatory roles of PAK1 and PAK3 in spine morphogenesis

Article Article scientifique Article Distinct, but compensatory roles of PAK1 and PAK3 in spine morphogenesis eng 2008 author Boda Bernadett 517654 author Jourdain Lorena 28062 author Muller Dominique 26488 857-861 10.1002/hipo.20451 18481281 1050-9631 PAK1 and PAK3 belong to a family of protein kinases that are effectors of small Rho GTPases. In humans, mutations of PAK3 have been associated with mental retardation and result in in vitro studies in defects of spine morphogenesis. The functional specificities of PAK1 and PAK3 remain, however, unclear. Here, we investigated using loss and gain of function experiments how PAK1 and PAK3 affect spine morphology in hippocampal slice cultures. We find that while knockdown of PAK3 is associated with an increase in thin, elongated, immature-type spines, downregulation of PAK1 does not alter spine morphology. Conversely, expression of a constitutively active form of PAK3 remains without effect, while expression of constitutively active PAK1 results in the formation of spines with smaller head diameters. Interestingly, expression of constitutively active PAK1 can rescue the long spine phenotype induced by suppression of PAK3. We conclude that while PAK1 and PAK3 share distinct roles in the regulation of spine morphogenesis, their activity may overlap allowing the compensation of the PAK3 deficit by PAK1. This result opens interesting perspectives in the context of reversing the spine defects associated with PAK3 mutations. Animals Dendritic Spines/physiology/ultrastructure Hippocampus/enzymology/growth & development/ultrastructure Mental Retardation/enzymology/pathology Morphogenesis/physiology Organ Culture Techniques RNA, Small Interfering/physiology Rats P21-Activated Kinases/physiology Dewey 616.8 53 Département de neurosciences fondamentales 21A false 53 Plasticité des synapses excitatrices 76 Hippocampus 18 9 428fe562-460d-4a72-9127-93443bd3af85 Article (Accepted version) Restricted Article.pdf 235670 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Distinct, but compensatory roles of PAK1 and PAK3 in spine morphogenesis	Hippocampus			2008	611	0

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Jourdain, Lorena