Dittmer TA, Misteli T.

	Figure 1. Nuclear lamins: domain organization and protein structure. (a) Domain organization of the major lamins in humans. The α-helical rod domain comprises four segments, 1A, 1B, 2A, 2B (yellow), which are separated by linker segments, L1, L12 and L2. The tail domain contains a nuclear localization signal, an immunoglobulin domain (green), and a conserved CAAX box, which undergoes farnesylation. (b) The structure of a portion of the α-helical rod domain corresponding to human lamin A segment 2B (PDB code: 1X8Y) [19]. (c) The structure of the Ig domain from human lamin A/C (PDB: 1IFR) [20].
	Figure 2. Phylogenetic relationships of metazoan lamins. An unrooted phylogenetic tree using an alignment of 31 lamin coding sequences [127]. Evolutionary history was inferred using the neighbor-joining method and evolutionary distances were computed using the maximum composite likelihood method [128,129]. The tree is drawn to scale with branch lengths proportional to the evolution distances. In general, all invertebrate lamins are B-type lamins. The exception is Drosophila LamC, which is considered an A-type lamin [130]. Vertebrate B-type lamins subdivide into three separate clades, B1, B2 and B3, the latter being specific to amphibians and fish. A-type lamins evolved from a Lamin B1-like ancestor and are unique to vertebrates. Major structural changes of lamins during evolution are indicated: the minus sign indicates a 90 amino acid deletion in the conserved Ig domain from tunicates (urochordate subphylum) [9]; the asterisk indicates the addition of 6 to 12 negatively charged amino acids within the tail domain of all lamins in the vertebrate lineage [9]; and the plus sign indicates the acquisition of an extra exon (exon 11), encoding 90 amino acids, in the tail domain of vertebrate A-type lamins [13].
	Figure 3. Schematic model of lamin polymers. Lamin dimers form from monomers that associate in a parallel, head-to-head manner, forming a coiled coil though the central α-helical domain. Lamin polymers then assemble by association of dimers in a polar head-to-tail manner through a staggered 2 to 4 nm overlap of the highly conserved amino- and carboxy-terminal rod domain ends. Protofilaments are finally produced through anti-parallel association of two lamin polymers. Between three and four protofilaments associate laterally to form an intermediate filament about 10 nm in diameter.
	Figure 4. Nuclear lamins: localization at the nuclear periphery and within the nucleoplasm. Immunofluorescence staining of lamin A/C (red) and lamin B1 (green) in U2OS human osteosarcoma cell and MEF cell nuclei, respectively.
	Figure 5. Functions of the nuclear lamina. A cartoon representation of the nuclear lamina, highlighting four key functions. (a) The lamina regulates genome organization and chromatin structure by direct interactions with chromatin and indirectly through association with chromatin-modifying and regulatory proteins. (b) The lamina regulates gene expression by sequestering transcription factors at the nuclear envelope, which limits their availability in the nucleoplasm. (c) It also mediates structural linkages between the nucleus and cytoskeleton, through the LINC complex consisting of lamins, an inner nuclear membrane protein, and an interacting outer nuclear membrane protein, which in turn binds cytoskeletal elements. (d) The lamina also provides a platform for assembly of protein complexes involved in signal transduction pathways. P, phosphate.
	Figure 6. Summary of disease-associated LMNA mutations mapped onto the human lamin A protein [110]. Colors indicate the class of disease. Red, laminopathies with preferential involvement of skeletal and cardiac muscle, which range from muscle-wasting muscular dystrophies to cardiac conduction defects; blue, lipodystrophies, which specifically affect adipose tissues; brown, neuropathy disorders, which affect the motor and sensory neurons of the peripheral nervous system; green, 'systemic' laminopathies, which are heterogeneous disorders involving multiple tissue systems; purple, mutations associated with premature aging disorders. Mutations affecting amino acids 1 to 566 affect both lamin A and C isoforms, whereas mutations found in the carboxy-terminal 566 to 664 amino acids are specific to the lamin A isoform. fs, frameshift; del, deletion; ins, insertion; c, coding.

Aaronson, Isolation of nuclear pore complexes in association with a lamina. 1975, Pubmed

Aaronson, Isolation of nuclear pore complexes in association with a lamina. 1975, Pubmed
Aebi, The nuclear lamina is a meshwork of intermediate-type filaments. , Pubmed , Xenbase
Akey, Interactions and structure of the nuclear pore complex revealed by cryo-electron microscopy. 1989, Pubmed , Xenbase
Andrés, Role of A-type lamins in signaling, transcription, and chromatin organization. 2009, Pubmed
Belmont, Lamin B distribution and association with peripheral chromatin revealed by optical sectioning and electron microscopy tomography. 1993, Pubmed
Benavente, Change of karyoskeleton during spermatogenesis of Xenopus: expression of lamin LIV, a nuclear lamina protein specific for the male germ line. 1985, Pubmed , Xenbase
Ben-Harush, The supramolecular organization of the C. elegans nuclear lamin filament. 2009, Pubmed
Bonne, Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. 1999, Pubmed
Bonne, LMNA mutations in atypical Werner's syndrome. 2003, Pubmed
Bossie, A cDNA from Drosophila melanogaster encodes a lamin C-like intermediate filament protein. 1993, Pubmed
Bridger, Internal lamin structures within G1 nuclei of human dermal fibroblasts. 1993, Pubmed
Broers, Partial cleavage of A-type lamins concurs with their total disintegration from the nuclear lamina during apoptosis. 2002, Pubmed
Broers, Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies. 2004, Pubmed
Broers, Nuclear A-type lamins are differentially expressed in human lung cancer subtypes. 1993, Pubmed
Broers, Dynamics of the nuclear lamina as monitored by GFP-tagged A-type lamins. 1999, Pubmed
Bruston, Loss of a DNA binding site within the tail of prelamin A contributes to altered heterochromatin anchorage by progerin. 2010, Pubmed
Burke, Life at the edge: the nuclear envelope and human disease. 2002, Pubmed
Coffinier, Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. 2010, Pubmed
Collas, Protein kinase C-mediated interphase lamin B phosphorylation and solubilization. 1997, Pubmed
Crisp, Coupling of the nucleus and cytoplasm: role of the LINC complex. 2006, Pubmed
Dahl, Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome. 2006, Pubmed
Daigle, Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells. 2001, Pubmed , Xenbase
Dhe-Paganon, Structure of the globular tail of nuclear lamin. 2002, Pubmed
Eggert, Identification of phosphorylation sites on murine nuclear lamin C by RP-HPLC and microsequencing. 1991, Pubmed
Erber, Characterization of the Hydra lamin and its gene: A molecular phylogeny of metazoan lamins. 1999, Pubmed
Fawcett, On the occurrence of a fibrous lamina on the inner aspect of the nuclear envelope in certain cells of vertebrates. 1966, Pubmed
Fisher, cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. 1986, Pubmed
Furukawa, Identification and cloning of an mRNA coding for a germ cell-specific A-type lamin in mice. 1994, Pubmed
Furukawa, cDNA cloning of a germ cell specific lamin B3 from mouse spermatocytes and analysis of its function by ectopic expression in somatic cells. 1993, Pubmed
Galiová, Chromatin changes induced by lamin A/C deficiency and the histone deacetylase inhibitor trichostatin A. 2008, Pubmed
Georgatos, Heterotypic and homotypic associations between the nuclear lamins: site-specificity and control by phosphorylation. 1988, Pubmed
Gerace, Immunocytochemical localization of the major polypeptides of the nuclear pore complex-lamina fraction. Interphase and mitotic distribution. 1978, Pubmed
Goldberg, Filaments made from A- and B-type lamins differ in structure and organization. 2008, Pubmed , Xenbase
Goldman, Pathway of incorporation of microinjected lamin A into the nuclear envelope. 1992, Pubmed
González, Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope. 2008, Pubmed
Granger, Modifier locus of the skeletal muscle involvement in Emery-Dreifuss muscular dystrophy. 2011, Pubmed
Guelen, Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. 2008, Pubmed
Håkelien, Expression of the myodystrophic R453W mutation of lamin A in C2C12 myoblasts causes promoter-specific and global epigenetic defects. 2008, Pubmed
Harborth, Identification of essential genes in cultured mammalian cells using small interfering RNAs. 2001, Pubmed
Hegele, Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. 2006, Pubmed
Hofemeister, Conservation of the gene structure and membrane-targeting signals of germ cell-specific lamin LIII in amphibians and fish. 2002, Pubmed , Xenbase
Hozák, Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. 1995, Pubmed
Ishikawa, Mitosis and intermediate-sized filaments in developing skeletal muscle. 1968, Pubmed
Isobe, The last twenty residues in the head domain of mouse lamin A contain important structural elements for formation of head-to-tail polymers in vitro. 2007, Pubmed
Johnson, A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. 2004, Pubmed
Kapinos, Characterization of the head-to-tail overlap complexes formed by human lamin A, B1 and B2 "half-minilamin" dimers. 2010, Pubmed
Karabinos, The single nuclear lamin of Caenorhabditis elegans forms in vitro stable intermediate filaments and paracrystals with a reduced axial periodicity. 2003, Pubmed
Kaufmann, Differential expression of nuclear envelope lamins A and C in human lung cancer cell lines. 1991, Pubmed
Kavanagh, Organelle proteome variation among different cell types: lessons from nuclear membrane proteins. 2007, Pubmed
Kennedy, Nuclear organization of DNA replication in primary mammalian cells. 2000, Pubmed
Krimm, The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy. 2002, Pubmed
Kubben, Mapping of protein- and chromatin-interactions at the nuclear lamina. 2010, Pubmed
Kumaran, Lamin A/C speckles mediate spatial organization of splicing factor compartments and RNA polymerase II transcription. 2002, Pubmed
Lammerding, Lamins A and C but not lamin B1 regulate nuclear mechanics. 2006, Pubmed
Lammerding, Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. 2004, Pubmed
Lazebnik, Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. 1995, Pubmed
Lehner, Differential expression of nuclear lamin proteins during chicken development. 1987, Pubmed , Xenbase
Levy, Nuclear size is regulated by importin α and Ntf2 in Xenopus. 2010, Pubmed , Xenbase
Lin, Structural organization of the human gene (LMNB1) encoding nuclear lamin B1. 1995, Pubmed , Xenbase
Lin, Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C. 1993, Pubmed , Xenbase
Lin, MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. 2005, Pubmed
Liu, Genomic instability in laminopathy-based premature aging. 2005, Pubmed
Ludérus, Binding of matrix attachment regions to lamin polymers involves single-stranded regions and the minor groove. 1994, Pubmed
Malhas, Lamin B1 controls oxidative stress responses via Oct-1. 2009, Pubmed
Malone, UNC-84 localizes to the nuclear envelope and is required for nuclear migration and anchoring during C. elegans development. 1999, Pubmed
Manju, Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. 2006, Pubmed
Marshall, A blood-based biomarker panel for stratifying current risk for colorectal cancer. 2010, Pubmed
McKeon, Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins. , Pubmed
Meier, The role of lamin LIII in nuclear assembly and DNA replication, in cell-free extracts of Xenopus eggs. 1991, Pubmed , Xenbase
Méjat, LINC complexes in health and disease. 2010, Pubmed
Moir, Dynamic properties of nuclear lamins: lamin B is associated with sites of DNA replication. 1994, Pubmed
Moir, Nuclear lamins A and B1: different pathways of assembly during nuclear envelope formation in living cells. 2000, Pubmed
Moir, Disruption of nuclear lamin organization blocks the elongation phase of DNA replication. 2000, Pubmed , Xenbase
Molloy, p34cdc2 kinase-mediated release of lamins from nuclear ghosts is inhibited by cAMP-dependent protein kinase. 1992, Pubmed , Xenbase
Moss, Decreased and aberrant nuclear lamin expression in gastrointestinal tract neoplasms. 1999, Pubmed
Newport, A lamin-independent pathway for nuclear envelope assembly. 1990, Pubmed , Xenbase
Nikolova, Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. 2004, Pubmed
Nindl, Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling. 2006, Pubmed
Oberhammer, Chromatin condensation during apoptosis is accompanied by degradation of lamin A+B, without enhanced activation of cdc2 kinase. 1994, Pubmed
Ognibene, Nuclear changes in a case of X-linked Emery-Dreifuss muscular dystrophy. 1999, Pubmed
Padiath, Lamin B1 duplications cause autosomal dominant leukodystrophy. 2006, Pubmed
Pajerowski, Physical plasticity of the nucleus in stem cell differentiation. 2007, Pubmed
Peter, In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. 1990, Pubmed
Prasad, Human Protein Reference Database and Human Proteinpedia as discovery tools for systems biology. 2009, Pubmed
Rankin, The laminopathies: a clinical review. 2006, Pubmed
Rao, Lamin proteolysis facilitates nuclear events during apoptosis. 1996, Pubmed
Riemer, The organization of the gene for Drosophila lamin C: limited homology with vertebrate lamin genes and lack of homology versus the Drosophila lamin Dmo gene. 1994, Pubmed
Riemer, Tunicates have unusual nuclear lamins with a large deletion in the carboxyterminal tail domain. 2000, Pubmed
Riemer, Common and variant properties of intermediate filament proteins from lower chordates and vertebrates; two proteins from the tunicate Styela and the identification of a type III homologue. 1998, Pubmed
Riemer, Analysis of the cDNA and gene encoding a cytoplasmic intermediate filament (IF) protein from the cephalochordate Branchiostoma lanceolatum; implications for the evolution of the IF protein family. 1992, Pubmed
Röber, Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study. 1989, Pubmed
Saitou, The neighbor-joining method: a new method for reconstructing phylogenetic trees. 1987, Pubmed
Scaffidi, Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. 2005, Pubmed
Scaffidi, Lamin A-dependent nuclear defects in human aging. 2006, Pubmed
Schatten, Nuclear lamins and peripheral nuclear antigens during fertilization and embryogenesis in mice and sea urchins. 1985, Pubmed
Schermelleh, Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy. 2008, Pubmed
Shimi, The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. 2008, Pubmed
Shoeman, The in vitro DNA-binding properties of purified nuclear lamin proteins and vimentin. 1990, Pubmed
Shumaker, The highly conserved nuclear lamin Ig-fold binds to PCNA: its role in DNA replication. 2008, Pubmed , Xenbase
Sinensky, The processing pathway of prelamin A. 1994, Pubmed
Skvortsov, Proteomics profiling of microdissected low- and high-grade prostate tumors identifies Lamin A as a discriminatory biomarker. 2011, Pubmed
Slee, Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. 2001, Pubmed
Spann, Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription. 2002, Pubmed , Xenbase
Spann, Disruption of nuclear lamin organization alters the distribution of replication factors and inhibits DNA synthesis. 1997, Pubmed , Xenbase
Starr, ANChors away: an actin based mechanism of nuclear positioning. 2003, Pubmed
Stewart, Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B. 1987, Pubmed
Stewart, Mouse models of the laminopathies. 2007, Pubmed
Stick, The gene structure of Xenopus nuclear lamin A: a model for the evolution of A-type from B-type lamins by exon shuffling. 1992, Pubmed , Xenbase
Strelkov, Crystal structure of the human lamin A coil 2B dimer: implications for the head-to-tail association of nuclear lamins. 2004, Pubmed
Sullivan, Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. 1999, Pubmed
Sun, Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients. 2010, Pubmed
Szeverenyi, The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases. 2008, Pubmed
Tamura, Prospects for inferring very large phylogenies by using the neighbor-joining method. 2004, Pubmed
Tamura, MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. 2007, Pubmed
Taniura, A chromatin binding site in the tail domain of nuclear lamins that interacts with core histones. 1995, Pubmed
Thompson, Identification of protein phosphatase 1 as a mitotic lamin phosphatase. 1997, Pubmed
Tilli, Lamin expression in normal human skin, actinic keratosis, squamous cell carcinoma and basal cell carcinoma. 2003, Pubmed
Van Berlo, A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors. 2005, Pubmed
Weber, Cytoplasmic intermediate filament proteins of invertebrates are closer to nuclear lamins than are vertebrate intermediate filament proteins; sequence characterization of two muscle proteins of a nematode. 1989, Pubmed
Wiesel, Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins. 2008, Pubmed
Willis, Lamin A/C is a risk biomarker in colorectal cancer. 2008, Pubmed
Wolin, A new lamin in Xenopus somatic tissues displays strong homology to human lamin A. 1987, Pubmed , Xenbase
Worman, "Laminopathies": a wide spectrum of human diseases. 2007, Pubmed
Worman, Nuclear lamina heterogeneity in mammalian cells. Differential expression of the major lamins and variations in lamin B phosphorylation. 1988, Pubmed
Worman, Diseases of the nuclear envelope. 2010, Pubmed
Yamaguchi, Identification and molecular cloning of germinal vesicle lamin B3 in goldfish (Carassius auratus) oocytes. 2001, Pubmed , Xenbase
Ye, Protein-protein interactions between human nuclear lamins expressed in yeast. 1995, Pubmed
Zastrow, Proteins that bind A-type lamins: integrating isolated clues. 2004, Pubmed
Zhang, Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies. 2008, Pubmed