The molecular architecture of lamins in somatic cells

Abstract

The nuclear lamina is a fundamental constituent of metazoan nuclei. It is composed mainly of lamins, which are intermediate filament proteins that assemble into a filamentous meshwork, bridging the nuclear envelope and chromatin 1–4. Besides providing structural stability to the nucleus 5,6, the lamina is involved in many nuclear activities, including chromatin organization, transcription and replication 7–10. However, the structural organization of the nuclear lamina is poorly understood. Here, we use cryo-electron tomography (cryo-ET) to obtain a detailed view of the organization of the lamin meshwork within the lamina. Data analysis of individual lamin filaments resolves a globular-decorated fiber appearance and shows that A- and B-type lamins assemble into tetrameric 3.5 nm thick filaments. Thus, lamins exhibit a structure that is remarkably different from the other canonical cytoskeletal elements. Our findings define the architecture of the nuclear lamin meshworks at molecular resolution, providing insights into their role in scaffolding the nuclear lamina.

Correlated Cryo Super‐Resolution Light and Cryo‐Electron Microscopy on Mammalian Cells Expressing the Fluorescent Protein rsEGFP2

“…Localizing individual or rare proteins and transient biomolecular complexes in situ using cryoEM is difficult due to the crowded cellular landscape that is visible by cryoEM. Currently, proteins are identified by, e.g., immunolabeling using gold beads, or tagged with proteins that accumulate heavy metals to become electron dense . However, these are not optimal, with generally a poor binding efficiency and difficulties with intracellular delivery of both heavy metals and (immuno)labeling agents .…”

Messages from the voices within: regulation of signaling by proteins of the nuclear lamina

“…The different lamin subtypes are assembled into structurally similar filaments that form a densely interwoven meshwork apposed to the INM [11,12]. Recent cryo-electron tomography revealed that lamin filaments in cultured cells are unexpectedly thin: they have an ~3.5 nm diameter, and most likely contain two dimers per filament cross-section [13 •• ]. By contrast, cytoplasmic intermediate filaments have a diameter of ~10 nm [14].…”

“…The diagram illustrates the direct connection of the ONM with the peripheral ER, and the lipid bilayer continuity between the ONM and INM at NPCs. Nuclear lamin filaments [13 •• ] are depicted as a green meshwork underlying the INM. Widely studied INM proteins are shown, with transmembrane segments and folded domains represented by cylinders spanning the lipid bilayer and external to it, respectively.…”

MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies

“…They bear an NLS leading to their importation into the nucleoplasm. In the nucleus, lamins A and C are constituents of the nuclear matrix: (i) the lamina where they interact with B‐type lamins, with several nuclear envelope transmembrane partner proteins (NETs) of the INM and with the NPC, and (ii) the internal nuclear meshwork forming a component of the nucleoskeleton (Cau et al., 2014; Gruenbaum & Foisner, 2015; Turgay et al., 2017). This lamin meshwork plays a major role in cell structure by conferring the architecture of the nucleoplasm and maintaining the nuclear shape (Ungricht & Kutay, 2017).…”