Scaffold, mechanics and functions of nuclear lamins

Abstract

Nuclear lamins are type‐V intermediate filaments that are involved in many nuclear processes. In mammals, A‐ and B‐type lamins assemble into separate physical meshwork underneath the inner nuclear membrane, the nuclear lamina, with some residual fraction localized within the nucleoplasm. Lamins are the major part of the nucleoskeleton, providing mechanical strength and flexibility to protect the genome and allow nuclear deformability, while also contributing to gene regulation via interactions with chromatin. While lamins are the evolutionary ancestors of all intermediate filament family proteins, their ultimate filamentous assembly is markedly different from their cytoplasmic counterparts. Interestingly, hundreds of genetic mutations in the lamina proteins have been causally linked with a broad range of human pathologies, termed laminopathies. These include muscular, neurological and metabolic disorders, as well as premature aging diseases. Recent technological advances have contributed to resolving the filamentous structure of lamins and the corresponding lamina organization. In this review, we revisit the multiscale lamin organization and discuss its implications on nuclear mechanics and chromatin organization within lamina‐associated domains.

Avian Influenza A Viruses Modulate the Cellular Cytoskeleton during Infection of Mammalian Hosts

“…A complex cytoskeletal network connects the plasma membrane to the nucleus and carries out diverse roles [ 54 ]. Specifically, the cytoskeleton contributes to cell morphology regulation, cell migration, apoptosis, cell differentiation, and cell division [ 52 , 55 , 56 , 57 , 58 , 59 ]. Importantly, all cytoskeletal components can swiftly adapt to both external and intracellular stimuli, undergoing rapid and continuous structural modifications [ 60 ].…”

N-terminal tags impair the ability of Lamin A to provide structural support to the nucleus

“…Lamins are nuclear intermediate filament proteins that form a dense protein meshwork underlying the inner nuclear membrane (Aebi et al, 1986; Buxboim et al, 2023; Shimi et al, 2015). Lamins have many important functions in metazoan cells, where they provide structural support to the nucleus and regulate nuclear morphology, contribute to nuclear mechanics, and influence gene expression (de Leeuw et al, 2018; Kalukula et al, 2022; Vahabikashi et al, 2022).…”

“…Lamins have many important functions in metazoan cells, where they provide structural support to the nucleus and regulate nuclear morphology, contribute to nuclear mechanics, and influence gene expression (de Leeuw et al, 2018; Kalukula et al, 2022; Vahabikashi et al, 2022). Vertebrate lamins are grouped into A-type and B-type lamins, which differ in their expression patterns, interaction partners, and effect on nuclear mechanical properties (Buxboim et al, 2023; Odell and Lammerding, 2023). Research on lamins frequently involves the addition of a tag, i.e., the fusion of a genetically encoded fluorophore or epitope tag to the lamin protein, to allow for detection in live cells and other assays, yet growing evidence suggests that the addition of tags may alter the behavior of the protein of interest.…”

Premature aging in genetic diseases: what conclusions can be drawn for physiological aging

“…HGPS as well as APS and MADA are caused by mutations in the LMNA gene that together with MADB, RD, and NGPS belong to a group of progeroid syndromes associated with defects in nuclear organization and stability ( Foo et al, 2019 ). LMNA gene encodes for the lamin A protein and an alternative splice variant lamin C, which together with lamins B1 and B2 constitute parts of a dense intermediate filament meshwork (type V) just beneath the inner nuclear membrane, the so called nuclear lamina ( Buxboim et al, 2023 ). Lamins are key nucleocytoskeletal connectors conferring shape and stability to the nucleus ( Osmanagic-Myers et al, 2015 ; Buxboim et al, 2023 ).…”

“…LMNA gene encodes for the lamin A protein and an alternative splice variant lamin C, which together with lamins B1 and B2 constitute parts of a dense intermediate filament meshwork (type V) just beneath the inner nuclear membrane, the so called nuclear lamina ( Buxboim et al, 2023 ). Lamins are key nucleocytoskeletal connectors conferring shape and stability to the nucleus ( Osmanagic-Myers et al, 2015 ; Buxboim et al, 2023 ). The role of lamins goes beyond a solely mechanical function and includes a plethothora of other tasks such as heterochromatin organization, scaffolding of transcriptional factors and affecting DNA replication and DNA repair as well ( Dechat et al, 2010 ; Gonzalo, 2014 ; Osmanagic-Myers and Foisner, 2019 ).…”