RGD Reference Report - Distinct, but compensatory roles of PAK1 and PAK3 in spine morphogenesis. - Rat Genome Database

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

Authors: Boda, B  Jourdain, L  Muller, D 
Citation: Boda B, etal., Hippocampus. 2008;18(9):857-61. doi: 10.1002/hipo.20451.
RGD ID: 7775053
Pubmed: PMID:18481281   (View Abstract at PubMed)
DOI: DOI:10.1002/hipo.20451   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Pak3Ratpositive regulation of dendritic spine morphogenesis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pak3  (p21 (RAC1) activated kinase 3)


Additional Information