Document Detail

Distinct, but compensatory roles of PAK1 and PAK3 in spine morphogenesis.
MedLine Citation:
PMID:  18481281     Owner:  NLM     Status:  MEDLINE    
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.
Bernadett Boda; Lorena Jourdain; Dominique Muller
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hippocampus     Volume:  18     ISSN:  1098-1063     ISO Abbreviation:  Hippocampus     Publication Date:  2008  
Date Detail:
Created Date:  2008-08-28     Completed Date:  2009-01-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9108167     Medline TA:  Hippocampus     Country:  United States    
Other Details:
Languages:  eng     Pagination:  857-61     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley-Liss, Inc.
Department of Basic Neuroscience, School of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
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MeSH Terms
Dendritic Spines / physiology*,  ultrastructure
Hippocampus / enzymology,  growth & development,  ultrastructure
Mental Retardation / enzymology,  pathology
Morphogenesis / physiology*
Organ Culture Techniques
RNA, Small Interfering / physiology
p21-Activated Kinases / physiology*
Reg. No./Substance:
0/Pak3 protein, rat; 0/RNA, Small Interfering; EC protein, rat; EC Kinases

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