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.

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