BIOMAT Database Logo BIOMAT Database Logo

Both lamin A and lamin C mutations cause lamina instability as well as loss of internal nuclear lamin organization. 2005

Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
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

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.

UI MeSH Term Description Entries
D009685 Nuclear Envelope The membrane system of the CELL NUCLEUS that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (NUCLEAR PORE). Nuclear Membrane,Envelope, Nuclear,Envelopes, Nuclear,Membrane, Nuclear,Membranes, Nuclear,Nuclear Envelopes,Nuclear Membranes
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002843 Chromatin The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell. Chromatins
D003923 Diabetes Mellitus, Lipoatrophic A type of diabetes mellitus that is characterized by severe INSULIN RESISTANCE and LIPODYSTROPHY. The latter may be generalized, partial, acquired, or congenital (LIPODYSTROPHY, CONGENITAL GENERALIZED). Lipoatrophic Diabetes,Diabete, Lipoatrophic,Diabetes, Lipoatrophic,Lipoatrophic Diabete,Lipoatrophic Diabetes Mellitus
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D016297 Mutagenesis, Site-Directed Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion. Mutagenesis, Oligonucleotide-Directed,Mutagenesis, Site-Specific,Oligonucleotide-Directed Mutagenesis,Site-Directed Mutagenesis,Site-Specific Mutagenesis,Mutageneses, Oligonucleotide-Directed,Mutageneses, Site-Directed,Mutageneses, Site-Specific,Mutagenesis, Oligonucleotide Directed,Mutagenesis, Site Directed,Mutagenesis, Site Specific,Oligonucleotide Directed Mutagenesis,Oligonucleotide-Directed Mutageneses,Site Directed Mutagenesis,Site Specific Mutagenesis,Site-Directed Mutageneses,Site-Specific Mutageneses

Related Publications

Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Nuclear shape is affected differentially by loss of lamin A, lamin C, or both lamin A and C.
January 2024, microPublication biology,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells.
February 1995, Journal of cell science,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Implications for nuclear organization and gene transcription of lamin A/C specific mutations.
January 2005, Advances in enzyme regulation,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C.
August 1993, The Journal of biological chemistry,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Nuclear pore protein TPR associates with lamin B1 and affects nuclear lamina organization and nuclear pore distribution.
June 2019, Cellular and molecular life sciences : CMLS,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis.
May 1990, Cell,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Both emerin and lamin C depend on lamin A for localization at the nuclear envelope.
July 2001, Journal of cell science,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
The nuclear lamina. Both a structural framework and a platform for genome organization.
March 2007, The FEBS journal,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects.
January 2013, Developmental biology,
Jos L V Broers, and H J H Kuijpers, and C Ostlund, and H J Worman, and J Endert, and F C S Ramaekers
Global loss of a nuclear lamina component, lamin A/C, and LINC complex components SUN1, SUN2, and nesprin-2 in breast cancer.
October 2015, Cancer medicine,
Copied contents to your clipboard!