Linked Life Data

15748902

Source:http://linkedlifedata.com/resource/pubmed/id/15748902

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-3-7
pubmed:abstractText
We have applied the fluorescence loss of intensity after photobleaching (FLIP) technique to study the molecular dynamics and organization of nuclear lamin proteins in cell lines stably transfected with green fluorescent protein (GFP)-tagged A-type lamin cDNA. Normal lamin A and C proteins show abundant decoration of the inner layer of the nuclear membrane, the nuclear lamina, and a generally diffuse localization in the nuclear interior. Bleaching studies revealed that, while the GFP-tagged lamins in the lamina were virtually immobile, the intranuclear fraction of these molecules was partially mobile. Intranuclear lamin C was significantly more mobile than intranuclear lamina A. In search of a structural cause for the variety of inherited diseases caused by A-type lamin mutations, we have studied the molecular organization of GFP-tagged lamin A and lamin C mutants R453W and R386K, found in Emery-Dreifuss muscular dystrophy (EDMD), and lamin A and lamin C mutant R482W, found in patients with Dunnigan-type familial partial lipodystrophy (FPLD). In all mutants, a prominent increase in lamin mobility was observed, indicating loss of structural stability of lamin polymers, both at the perinuclear lamina and in the intranuclear lamin organization. While the lamin rod domain mutant showed overall increased mobility, the tail domain mutants showed mainly intranuclear destabilization, possibly as a result of loss of interaction with chromatin. Decreased stability of lamin mutant polymers was confirmed by flow cytometric analyses and immunoblotting of nuclear extracts. Our findings suggest a loss of function of A-type lamin mutant proteins in the organization of intranuclear chromatin and predict the loss of gene regulatory function in laminopathies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
304
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
582-92
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:15748902-Animals, pubmed-meshheading:15748902-CHO Cells, pubmed-meshheading:15748902-Cell Nucleus, pubmed-meshheading:15748902-Chromatin, pubmed-meshheading:15748902-Cricetinae, pubmed-meshheading:15748902-DNA, Complementary, pubmed-meshheading:15748902-Diabetes Mellitus, Lipoatrophic, pubmed-meshheading:15748902-Fluorescence Recovery After Photobleaching, pubmed-meshheading:15748902-Green Fluorescent Proteins, pubmed-meshheading:15748902-Humans, pubmed-meshheading:15748902-Lamin Type A, pubmed-meshheading:15748902-Muscular Dystrophy, Emery-Dreifuss, pubmed-meshheading:15748902-Mutagenesis, Site-Directed, pubmed-meshheading:15748902-Nuclear Envelope, pubmed-meshheading:15748902-Nuclear Proteins, pubmed-meshheading:15748902-Protein Transport, pubmed-meshheading:15748902-Transfection
pubmed:year
2005
pubmed:articleTitle
Both lamin A and lamin C mutations cause lamina instability as well as loss of internal nuclear lamin organization.
pubmed:affiliation
Department of Molecular Cell Biology, Box 17, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, PO Box 616, NL-6200 MD Maastricht, The Netherlands. jos.broers@molcelb.unimaas.nl
pubmed:publicationType
Journal Article