Scaffold, mechanics and functions of nuclear lamins

• Published in: FEBS letters Vol. 597; no. 22; pp. 2791 - 2805
• Main Authors: Buxboim, Amnon, Kronenberg‐Tenga, Rafael, Salajkova, Sarka, Avidan, Nili, Shahak, Hen, Thurston, Alice, Medalia, Ohad
• Format: Journal Article
• Language: English
• Published: England 01.11.2023
• Subjects: Animals; Cell Nucleus - metabolism; chromatin; Chromatin - metabolism; genes; genetic disorders; Humans; intermediate filaments; Intermediate Filaments - metabolism; lamins; Lamins - chemistry; Lamins - genetics; Lamins - metabolism; Mammals - genetics; Mammals - metabolism; mechanobiology; Nuclear Envelope; nuclear lamina; Nuclear Lamina - metabolism; nuclear membrane; progeria; strength (mechanics); mechanobiology; progeria; nuclear lamina; lamins; intermediate filaments
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.14750

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. Nuclear lamins, constituents of the nuclear lamina, bridge the gap between the nuclear membranes and chromatin. Here, we discuss the lamins' structure, assembly dynamics and their interactions with chromatin. We focus on the mechanical roles of lamins, from molecular to network scales, and finalize by linking the structural, mechanical, and molecular properties of lamins with biological function and disease.