The Ig-like Structure of the C-Terminal Domain of Lamin A/C, Mutated in Muscular Dystrophies, Cardiomyopathy, and Partial Lipodystrophy

Krimm, Isabelle; Östlund, Cecilia; Gilquin, Bernard; Couprie, Joël; Hossenlopp, Paul; Mornon, Jean‐Paul; Bonne, Gisèle; Courvalin, Jean-Claude; Worman, Howard J.; Zinn‐Justin, Sophie

doi:10.1016/s0969-2126(02)00777-3

Cited by 260 publications

(315 citation statements)

References 45 publications

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“…Less chromatin in regions of the nucleus could conceivably enhance exposure of the nucleoplasmic face of the inner nuclear membrane and thereby facilitate the egress of nucleocapsids. Since amino acids 411 to 553 of lamin A/C comprise a globular DNA binding domain that helps mediate association with chromatin (5,13,17,28,30), it was of interest that, through epitope mapping and GST pulldown reactions, we have determined that amino acids in or near the lamin A tail domain (amino acids 369 to 519 and 490 to 660) are sufficient to interact with U L 31 protein.…”

Section: Discussionmentioning

confidence: 99%

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Reynolds

Liang

Baines

2004

J Virol

159

209

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The herpes simplex virus type 1 (HSV-1) U L 31 and U L 34 proteins are dependent on each other for proper targeting to the nuclear membrane and are required for efficient envelopment of nucleocapsids at the inner nuclear membrane. In this work, we show that whereas the solubility of lamins A and C (lamin A/C) was not markedly increased, HSV induced conformational changes in the nuclear lamina of infected cells, as viewed after staining with three different lamin A/C-specific antibodies. In one case, reactivity with a monoclonal antibody that recognizes an epitope in the lamin tail domain was greatly reduced in HSV-infected cells. This apparent HSV-induced epitope masking required both U L 31 and U L 34, but these proteins were not sufficient to mask the epitope in uninfected cells, indicating that other HSV proteins are also required. In the second case, staining with a rabbit polyclonal antibody that primarily recognizes epitopes in the lamin A/C rod domain revealed that U L 34 is required for HSV-induced decreased availability of epitopes for reaction with the antibody, whereas U L 31 protein was dispensable for this effect. Still another polyclonal antibody indicated virtually no difference in lamin A/C staining in infected versus uninfected cells, indicating that the HSVinduced changes are more conformational than the result of lamin depletion at the nuclear rim. Further evidence supporting an interaction between the nuclear lamina and the U L 31/U L 34 protein complex includes the observations that (i) overexpression of the U L 31 protein in uninfected cells was sufficient to relocalize lamin A/C from the nuclear rim into nucleoplasmic aggregates, (ii) overexpression of U L 34 was sufficient to relocalize some lamin A/C into the cytoplasm, and (iii) both U L 31 and U L 34 could directly bind lamin A/C in vitro. These studies suggest that the U L 31 and U L 34 proteins modify the conformation of the nuclear lamina in infected cells, possibly by direct interaction with lamin A/C, and that other proteins are also likely involved. Given that the nuclear lamina potentially excludes nucleocapsids from envelopment sites at the inner nuclear membrane, the lamina alteration may reflect a role of the U L 31/U L 34 protein complex in perturbing the lamina to promote nucleocapsid egress from the nucleus. Alternatively, the data are compatible with a role of the lamina in targeting the U L 31/U L 34 protein complex to the nuclear membrane.The nuclear envelope consists of two leaflets, defined as the inner nuclear membrane and outer nuclear membrane. The perinuclear space, defined as the space between the two leaflets, is continuous with the lumen of the endoplasmic reticulum. A network of predominantly insoluble cellular proteins, the nuclear lamina, lines the nucleoplasmic face of the inner nuclear membrane. The nuclear lamina provides structural support for the nuclear membrane and attachment sites for chromatin. It is also required for a variety of essential cellular functions, including nuclear assembly following mi...

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Section: Discussionmentioning

confidence: 99%

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Reynolds

Liang

Baines

2004

J Virol

159

209

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“…High numbers of mutations in the tail domain have only been recorded in the lamins (200/232): lamins have several important functional motifs in their tail domains, including a nuclear localization signal (NLS), a region with immunoglobulin-like structure and a CaaX motif for membrane anchorage modifications. Sequence variation in the NLS results in aberrant filament assembly in the cytoplasm, and mutations affecting the Ig-like structure or the CaaX-dependent posttranslational processing have been directly associated with laminopathies [Krimm et al, 2002;Loewinger and McKeon, 1988].…”

Section: Analysis Of Datasetsmentioning

confidence: 99%

The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

et al. 2008

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Communicated by A. Jamie CuticchiaWe describe a revised and expanded database on human intermediate filament proteins, a major component of the eukaryotic cytoskeleton. The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. To date, the database catalogs 1,274 manually-curated pathogenic sequence variants and 170 allelic variants in intermediate filament genes from over 459 peer-reviewed research articles. Unrelated cases were collected from all of the six sequence homology groups and the sequence variations were described at cDNA and protein levels with links to the related diseases and reference articles. The mutations and polymorphisms are presented in parallel with data on protein structure, gene, and chromosomal location and basic information on associated diseases. Detailed statistics relating to the variants records in the database are displayed by homology group, mutation type, affected domain, associated diseases, and nucleic and amino acid substitutions. Multiple sequence alignment algorithms can be run from queries to determine DNA or protein sequence conservation. Literature sources can be interrogated within the database and external links are provided to public databases. The database is freely and publicly accessible online at www.interfil.org (last accessed 13 September 2007). Users can query the database by various keywords and the search results can be downloaded. It is anticipated that the Human Intermediate Filament Database (HIFD) will provide a useful resource to study human genome variations for basic scientists, clinicians, and students alike. Hum Mutat 29(3), [351][352][353][354][355][356][357][358][359][360] 2008.

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“…In addition, the mutations could disrupt interactions between the lamins and chromatin or other nuclear proteins. Indeed it has been suggested that mutations in the carboxy globular domain that cause FPLD and MAD are due to perturbations in the interactions between Lamin A and other proteins, such as the cholesterol synthesis regulator SREBP1 [36][37][38].…”

Section: ´3tmentioning

confidence: 99%

Aging and nuclear organization: lamins and progeria

Mounkes

Stewart

2004

Current Opinion in Cell Biology

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The Ig-like Structure of the C-Terminal Domain of Lamin A/C, Mutated in Muscular Dystrophies, Cardiomyopathy, and Partial Lipodystrophy

Cited by 260 publications

References 45 publications

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

Aging and nuclear organization: lamins and progeria

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The Ig-like Structure of the C-Terminal Domain of Lamin A/C, Mutated in Muscular Dystrophies, Cardiomyopathy, and Partial Lipodystrophy

Cited by 260 publications

References 45 publications

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U L 31 and U L 34

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U L 31 and U L 34

The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

Aging and nuclear organization: lamins and progeria

Contact Info

Product

Resources

About

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34