The nuclear lamina comes of age

A- and B-type lamins form stable filaments in the nucleus, which anchor many nuclear-membrane proteins, soluble proteins and multiprotein complexes.Lamins are needed directly or indirectly for many roles including the mechanical stability and shape of the nucleus, DNA replication and transcription, chromatin organization, cell-cycle regulation, cell development and differentiation, nuclear anchoring and migration, centrosome positioning and apoptosis. Each role probably involves one or more specific lamin-dependent complexes.Mutations in A-type lamins (LMNA), or lamin-binding membrane proteins such as emerin or lamin-B receptor (LBR), cause heritable human diseases (laminopathies), which include muscular dystrophy, cardiomyopathy and accelerated ageing (progeria) syndromes. Diseases are proposed to arise from the defective assembly or function of the lamin-dependent protein complexes that are important for each affected tissue.LBR, which is embedded in the inner nuclear membrane by eight transmembrane spans, binds lamins and has an essential sterol-reductase activity. LBR protein also functions as a scaffold for proteins (such as HP1) that are involved in chromatin silencing.LEM-domain proteins (such as emerin, MAN1 and LAP2) bind lamins and function as scaffolds for various proteins including transcription regulators, such as germ cell-less (GCL) and BCL2-associated transcription factor (BTF); chromatin proteins, such as barrier-to-autointegration factor (BAF); and proteins that respond to TGFβ signalling, such as SMADs. Emerin also caps the pointed (minus) ends of filamentous (F)-actin in vitro, which indicates that it has roles in nuclear architecture.Two emerging protein families, nesprins and SUN (Sad1/UNC-84 homology)-domain proteins, localize specifically to the inner or outer nuclear membrane, and interact with each other to form proposed 'bridging' complexes that span the nuclear envelope. These lamin-dependent complexes attach to cytoplasmic actin filaments, microtubules, or centrosomes, and mediate changes in nuclear position (for example, during development).