Linked Life Data

19084535

Source:http://linkedlifedata.com/resource/pubmed/id/19084535

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-1-19
pubmed:abstractText
Ezrin, radixin and moesin are a family of proteins that provide a link between the plasma membrane and the cortical actin cytoskeleton. The regulated targeting of ezrin to the plasma membrane and its association with cortical F-actin are more than likely functions necessary for a number of cellular processes, such as cell adhesion, motility, morphogenesis and cell signalling. The interaction with F-actin was originally mapped to the last 34 residues of ezrin, which correspond to the last three helices (alphaB, alphaC and alphaD) of the C-terminal tail. We set out to identify and mutate the ezrin/F-actin binding site in order to pinpoint the role of F-actin interaction in morphological processes as well as signal transduction. We report here the generation of an ezrin mutant defective in F-actin binding. We identified four actin-binding residues, T576, K577, R579 and I580, that form a contiguous patch on the surface of the last helix, alphaD. Interestingly, mutagenesis of R579 also eliminated the interaction of band four-point one, ezrin, radixin, moesin homology domains (FERM) and the C-terminal tail domain, identifying a hotspot of the FERM/tail interaction. In vivo expression of the ezrin mutant defective in F-actin binding and FERM/tail interaction (R579A) altered the normal cell surface structure dramatically and inhibited cell migration. Further, we showed that ezrin/F-actin binding is required for the receptor tyrosine kinase signal transfer to the Ras/MAP kinase signalling pathway. Taken together, these observations highlight the importance of ezrin/F-actin function in the development of dynamic membrane/actin structures critical for cell shape and motility, as well as signal transduction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
385
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1015-31
pubmed:meshHeading
pubmed-meshheading:19084535-Actins, pubmed-meshheading:19084535-Amino Acid Sequence, pubmed-meshheading:19084535-Amino Acid Substitution, pubmed-meshheading:19084535-Amino Acids, pubmed-meshheading:19084535-Animals, pubmed-meshheading:19084535-Cell Membrane, pubmed-meshheading:19084535-Cytoskeletal Proteins, pubmed-meshheading:19084535-Humans, pubmed-meshheading:19084535-Membrane Proteins, pubmed-meshheading:19084535-Mice, pubmed-meshheading:19084535-Microfilament Proteins, pubmed-meshheading:19084535-Models, Molecular, pubmed-meshheading:19084535-Molecular Sequence Data, pubmed-meshheading:19084535-Mutagenesis, Site-Directed, pubmed-meshheading:19084535-Mutant Proteins, pubmed-meshheading:19084535-NIH 3T3 Cells, pubmed-meshheading:19084535-Phosphorylation, pubmed-meshheading:19084535-Phosphothreonine, pubmed-meshheading:19084535-Point Mutation, pubmed-meshheading:19084535-Protein Binding, pubmed-meshheading:19084535-Protein Structure, Secondary, pubmed-meshheading:19084535-Protein Transport, pubmed-meshheading:19084535-Sus scrofa
pubmed:year
2009
pubmed:articleTitle
Properties of an ezrin mutant defective in F-actin binding.
pubmed:affiliation
Leibniz Institute of Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't