Scientific article
Open access

Sequential implication of the mental retardation proteins ARHGEF6 and PAK3 in spine morphogenesis

Published inJournal of cell science, vol. 119, no. Pt 23, p. 4986-4993
Publication date2006

The biological mechanisms underlying the mental retardation associated with mutation of the ARHGEF6 gene, a Rac1/Cdc42 exchange factor, are still unknown, although defects in the plasticity of synaptic networks have been postulated. We have cloned the rat ARHGEF6 gene and investigated, using a transfection approach, its involvement in spine morphogenesis and its relationship to p21-activated kinase 3 (PAK3). We found that expression of tagged ARHGEF6 in hippocampal slice cultures shows a punctate staining in dendritic spines that colocalizes with PSD95. Over-expression of ARHGEF6, of PAK3 or constitutively active PAK3 did not alter spine morphology. By contrast, knockdown of ARHGEF6 using a siRNA approach resulted in abnormalities in spine morphology similar to those reported with knockdown of PAK3. This phenotype could be rescued through co-expression of a constitutively active PAK3 protein, but not with wild-type PAK3. Together, these results indicate that ARHGEF6 is localized in dendritic spines where it contributes to regulate spine morphogenesis probably by acting through a downstream activation of PAK3. Similar mechanisms are thus likely to underlie the mental retardation induced by mutations of ARHGEF6 and PAK3.

  • Animals
  • Cell Cycle Proteins/antagonists & inhibitors/genetics/metabolism/ physiology
  • Dendritic Spines/ genetics/metabolism
  • Guanine Nucleotide Exchange Factors/antagonists &
  • Inhibitors/genetics/metabolism/ physiology
  • Hippocampus/cytology/metabolism
  • Mental Retardation/genetics
  • Mice
  • NIH 3T3 Cells
  • Phenotype
  • Protein-Serine-Threonine Kinases/antagonists &
  • Inhibitors/genetics/metabolism/ physiology
  • RNA, Small Interfering/pharmacology
  • Rats
  • Time Factors
  • Tissue Culture Techniques
  • Transfection
  • P21-Activated Kinases
Citation (ISO format)
NODÉ-LANGLOIS, Roxanne, MULLER, Dominique, BODA, Bernadett. Sequential implication of the mental retardation proteins ARHGEF6 and PAK3 in spine morphogenesis. In: Journal of cell science, 2006, vol. 119, n° Pt 23, p. 4986–4993. doi: 10.1242/jcs.03273
Updates (1)
ISSN of the journal0021-9533

Technical informations

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