Linked Life Data

9425229

Source:http://linkedlifedata.com/resource/pubmed/id/9425229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-3-17
pubmed:abstractText
Although schwannomin, the product of the neurofibromatosis type 2 gene, shares homology with three cytoskeleton-to-membrane protein linkers defining the ERM family, the mechanism by which it exerts a tumor suppressive activity remains elusive. Based on the knowledge of naturally occurring mutations, a functional study of schwannomin was initiated. Constructs encoding the two wild-type isoforms and nine mutant forms were transfected into HeLa cells. Transiently expressed wild-type isoforms were both observed underneath the plasma membrane. At this location they were detergent insoluble and redistributed by a cytochalasin D treatment, suggesting interaction with actin-based cytoskeletal structures. Proteins with single amino acid substitutions at positions 219 and 220 demonstrated identical properties. Three different truncated schwannomins, that are prototypic for most naturally occurring NF2 mutations, were affected neither in their location nor in their cytochalasin D sensitivity. However, they were revealed to be detergent soluble, indicating a relaxed interaction with the actin-based structures. An increased solubility was also observed for a mutant with a single amino acid substitution at position 360 in the C-terminal half of the protein. Mutant proteins with either a single amino acid deletion at position 118 or an 83 amino acid deletion within the N-terminal domain had lost the submembraneous localization and tended to accumulate in perinuclear patches that were unaffected by cytochalasin D treatment. A similar behavior was observed when the N-terminal domain was entirely deleted. Taken together these observations suggest that the N-terminal domain is the main determinant that localizes the protein at the membrane where it interacts weakly with actin-based cytoskeletal structures. The C-terminal domain potentiates this interaction. With rare exceptions, most naturally occurring mutant schwannomins that have lost their tumor suppressive activity are impaired in an interaction involving actin-based structures and are no longer firmly maintained at the membrane.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
217-26
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9425229-Actins, pubmed-meshheading:9425229-Cell Membrane, pubmed-meshheading:9425229-Cytochalasin D, pubmed-meshheading:9425229-Cytoskeleton, pubmed-meshheading:9425229-Detergents, pubmed-meshheading:9425229-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:9425229-Genes, Neurofibromatosis 2, pubmed-meshheading:9425229-HeLa Cells, pubmed-meshheading:9425229-Humans, pubmed-meshheading:9425229-Membrane Proteins, pubmed-meshheading:9425229-Microscopy, Immunoelectron, pubmed-meshheading:9425229-Neurofibromin 2, pubmed-meshheading:9425229-Nocodazole, pubmed-meshheading:9425229-Point Mutation, pubmed-meshheading:9425229-Protein Binding, pubmed-meshheading:9425229-Recombinant Fusion Proteins, pubmed-meshheading:9425229-Sequence Deletion, pubmed-meshheading:9425229-Solubility, pubmed-meshheading:9425229-Structure-Activity Relationship, pubmed-meshheading:9425229-Subcellular Fractions, pubmed-meshheading:9425229-Transfection
pubmed:year
1998
pubmed:articleTitle
Impaired interaction of naturally occurring mutant NF2 protein with actin-based cytoskeleton and membrane.
pubmed:affiliation
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't