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#nuclear lamina

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Cell Organelles

The nuclear lamina is composed of:

Meshwork underlying inner nuclear membrane known as nuclear lamina provides mechanical strength preventing envelope rupture under cytoskeletal tension transmitted via LINC complex and organizes chromatin positioning. It consists of intermediate filament proteins lamins subclassified into B-type encoded by LMNB1 and LMNB2 constitutively farnesylated for membrane anchorage, and A-type encoded by LMNA via alternative splicing producing lamin A including farnesylated precursor processed to mature form and lamin C lacking farnesylation, expressed after differentiation. Lamins assemble via parallel coiled-coil dimers forming head-to-tail polymers assembling into ten nanometer filaments forming orthogonal lattice. They interact with integral membrane proteins emerin, LAP2beta, LBR and chromatin adaptor BAF. Phosphorylation by CDK1 at mitosis drives depolymerization allowing envelope breakdown. Tubulin forms twenty five nanometer microtubules, actin seven nanometer microfilaments, spectrin and ankyrin support erythrocyte membrane, histone H1 compacts linkers between nucleosomes, therefore not components of lamina lattice. Mutations cause progeria and muscular dystrophies. Integration with cell cycle kinases, calcium signaling and mechanical cues ensures coordinated remodeling during growth, migration and differentiation.

Ref: Burke Annu Rev Cell Dev Biol; lamins A/B/C type V IF, farnesylation, lattice under inner membrane.

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Cytoskeleton

What is the function of the nuclear lamina?

Interphase nucleus experiences mechanical stresses from cytoskeletal pulling forces migration through constricted spaces and chromatin dynamics requiring reinforcement beyond lipid bilayer envelope alone. Nuclear lamina provides mechanical support as dense meshwork 10 to 20 nm thick apposed to inner nuclear membrane beneath lamina associated chromatin domains. Composed of A type lamins lamin A and C splice isoforms and B type lamins B1 B2 type V intermediate filament proteins forming coiled coil dimers assembling head to tail polymers into orthogonal filaments crosslinked into sheet. Mesh confers elastic stiffness about 2 to 5 fold increasing nuclear rigidity buffers deformation prevents rupture under high strain anchors nuclear pore complexes basket tethers lamina associated domains LADs enriched heterochromatin regulating transcription silencing. Additional functions include mechanotransduction signaling via emerin to regulate gene expression and DNA repair scaffolding through 53BP1. Disassembly mediated by CDK1 phosphorylation disassembles filaments during mitosis enabling nuclear envelope breakdown chromosome capture. Additional regulatory inputs including phosphorylation, small GTPases, and cargo adaptors fine tune filament assembly stability and motor activity matching cellular demands during division, migration, and mechanical stress responses efficiently.

Ref: Dechat et al., Genes Dev 2008 – Nuclear lamina provides mechanical support to nucleus function.

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