Document Detail


A dual role for Rac1 GTPases in the regulation of cell motility.
MedLine Citation:
PMID:  22302991     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rac proteins are the only canonical Rho family GTPases in Dictyostelium, where they act as key regulators of the actin cytoskeleton. To monitor the dynamics of activated Rac1 in Dictyostelium cells, a fluorescent probe was developed that specifically binds to the GTP-bound form of Rac1. The probe is based on the GTPase-binding domain (GBD) from PAK1 kinase, and was selected on the basis of yeast two-hybrid, GST pull-down and fluorescence resonance energy transfer assays. The PAK1 GBD localizes to leading edges of migrating cells and to endocytotic cups. Similarly to its role in vertebrates, activated Rac1 therefore appears to control de novo actin polymerization at protruding regions of the Dictyostelium cell. Additionally, we found that the IQGAP-related protein DGAP1, which sequesters active Rac1 into a quaternary complex with actin-binding proteins cortexillin I and cortexillin II, localizes to the trailing regions of migrating cells. Notably, PAK1 GBD and DGAP1, which both bind to Rac1-GTP, display mutually exclusive localizations in cell migration, phagocytosis and cytokinesis, and opposite dynamics of recruitment to the cell cortex upon stimulation with chemoattractants. Moreover, cortical localization of the PAK1 GBD depends on the integrity of the actin cytoskeleton, whereas cortical localization of DGAP1 does not. Taken together, these results imply that Rac1 GTPases play a dual role in regulation of cell motility and polarity in Dictyostelium.
Authors:
Vedrana Filić; Maja Marinović; Jan Faix; Igor Weber
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-02
Journal Detail:
Title:  Journal of cell science     Volume:  125     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-02-23     Completed Date:  2013-04-04     Revised Date:  2013-09-06    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  387-98     Citation Subset:  IM    
Affiliation:
Ruder Bošković Institute, Division of Molecular Biology, Bijenička 54, HR-10000 Zagreb, Croatia.
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / metabolism
Bicyclo Compounds, Heterocyclic / pharmacology
Cell Line
Cell Movement*
Cyclic AMP / metabolism
Dictyostelium / enzymology,  metabolism,  physiology
Fluorescence Resonance Energy Transfer
Fluorescent Dyes
Folic Acid / pharmacology
GTPase-Activating Proteins / metabolism
Protein Interaction Domains and Motifs
Thiazolidines / pharmacology
p21-Activated Kinases / chemistry,  metabolism
rac1 GTP-Binding Protein / analysis,  metabolism,  physiology*
Chemical
Reg. No./Substance:
0/Bicyclo Compounds, Heterocyclic; 0/Fluorescent Dyes; 0/GTPase-Activating Proteins; 0/Thiazolidines; 59-30-3/Folic Acid; 60-92-4/Cyclic AMP; 76343-94-7/latrunculin B; EC 2.7.11.1/p21-Activated Kinases; EC 3.6.5.2/rac1 GTP-Binding Protein
Comments/Corrections
Comment In:
Small GTPases. 2013 Apr-Jun;4(2):110-5   [PMID:  23503127 ]

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