Editorial

2 pages, 196 KiB

Open AccessEditorial

Nuclear Shape-Shifters: Lipid and Protein Dynamics at the Nuclear Envelope

by Wolfram Antonin and Symeon Siniossoglou

Cells 2022, 11(24), 4120; https://doi.org/10.3390/cells11244120 - 19 Dec 2022

Viewed by 1269

The nuclear envelope constitutes a selective barrier that segregates chromatin into the nucleus of eukaryotic cells [...] Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

Research

Jump to: Editorial, Review

17 pages, 3027 KiB

Open AccessArticle

Nuclear Lipid Droplet Birth during Replicative Stress

by Sylvain Kumanski, Romain Forey, Chantal Cazevieille and María Moriel-Carretero

Cells 2022, 11(9), 1390; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11091390 - 20 Apr 2022

Cited by 8 | Viewed by 2476

Abstract

The nuclear membrane defines the boundaries that confine, protect and shape the genome. As such, its blebbing, ruptures and deformations are known to compromise the integrity of genetic material. Yet, drastic transitions of the nuclear membrane such as its invagination towards the nucleoplasm [...] Read more.

The nuclear membrane defines the boundaries that confine, protect and shape the genome. As such, its blebbing, ruptures and deformations are known to compromise the integrity of genetic material. Yet, drastic transitions of the nuclear membrane such as its invagination towards the nucleoplasm or its capacity to emit nuclear lipid droplets (nLD) have not been evaluated with respect to their impact on genome dynamics. To begin assessing this, in this work we used Saccharomyces cerevisiae as a model to ask whether a selection of genotoxins can trigger the formation of nLD. We report that nLD formation is not a general feature of all genotoxins, but of those engendering replication stress. Exacerbation of endogenous replication stress by genetic tools also elicited nLD formation. When exploring the lipid features of the nuclear membrane at the base of this emission, we revealed a link with the unsaturation profile of its phospholipids and, for the first time, of its sterol content. We propose that stressed replication forks may stimulate nLD birth by anchoring to the inner nuclear membrane, provided that the lipid context is adequate. Further, we point to a transcriptional feed-back process that counteracts the membrane’s proneness to emit nLD. With nLD representing platforms onto which genome-modifying reactions can occur, our findings highlight them as important players in the response to replication stress. Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

► Show Figures

Figure 1

21 pages, 3773 KiB

Open AccessArticle

Mechanisms of A-Type Lamin Targeting to Nuclear Ruptures Are Disrupted in LMNA- and BANF1-Associated Progerias

by Rhiannon M. Sears and Kyle J. Roux

Cells 2022, 11(5), 865; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11050865 - 02 Mar 2022

Cited by 8 | Viewed by 3637

Abstract

Mutations in the genes LMNA and BANF1 can lead to accelerated aging syndromes called progeria. The protein products of these genes, A-type lamins and BAF, respectively, are nuclear envelope (NE) proteins that interact and participate in various cellular processes, including nuclear envelope rupture [...] Read more.

Mutations in the genes LMNA and BANF1 can lead to accelerated aging syndromes called progeria. The protein products of these genes, A-type lamins and BAF, respectively, are nuclear envelope (NE) proteins that interact and participate in various cellular processes, including nuclear envelope rupture and repair. BAF localizes to sites of nuclear rupture and recruits NE-repair machinery, including the LEM-domain proteins, ESCRT-III complex, A-type lamins, and membranes. Here, we show that it is a mobile, nucleoplasmic population of A-type lamins that is rapidly recruited to ruptures in a BAF-dependent manner via BAF’s association with the Ig-like β fold domain of A-type lamins. These initially mobile lamins become progressively stabilized at the site of rupture. Farnesylated prelamin A and lamin B1 fail to localize to nuclear ruptures, unless that farnesylation is inhibited. Progeria-associated LMNA mutations inhibit the recruitment affected A-type lamin to nuclear ruptures, due to either permanent farnesylation or inhibition of BAF binding. A progeria-associated BAF mutant targets to nuclear ruptures but is unable to recruit A-type lamins. Together, these data reveal the mechanisms that determine how lamins respond to nuclear ruptures and how progeric mutations of LMNA and BANF1 impair recruitment of A-type lamins to nuclear ruptures. Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

► Show Figures

Figure 1

12 pages, 3742 KiB

Open AccessArticle

Proximity Ligation Mapping of Microcephaly Associated SMPD4 Shows Association with Components of the Nuclear Pore Membrane

by Alexandra C. A. Piët, Marco Post, Dick Dekkers, Jeroen A. A. Demmers and Maarten Fornerod

Cells 2022, 11(4), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11040674 - 15 Feb 2022

Cited by 3 | Viewed by 2335

Abstract

SMPD4 is a neutral sphingomyelinase implicated in a specific type of congenital microcephaly. Although not intensively studied, SMPD4 deficiency has also been found to cause cell division defects. This suggests a role for SMPD4 in cell-cycle and differentiation. In order to explore this [...] Read more.

SMPD4 is a neutral sphingomyelinase implicated in a specific type of congenital microcephaly. Although not intensively studied, SMPD4 deficiency has also been found to cause cell division defects. This suggests a role for SMPD4 in cell-cycle and differentiation. In order to explore this role, we used proximity ligation to identify the partners of SMPD4 in vivo in HEK293T cells. We found that these partners localize near the endoplasmic reticulum (ER) and the nuclear membrane. Using mass spectrometry, we could identify these partners and discovered that SMPD4 is closely associated with several nucleoporins, including NUP35, a nucleoporin directly involved in pore membrane curvature and pore insertion. This suggests that SMPD4 may play a role in this process. Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

► Show Figures

Figure 1

14 pages, 4843 KiB

Open AccessArticle

Partial Disassembly of the Nuclear Pore Complex Proteins during Semi-Closed Mitosis in Dictyostelium discoideum

by Kristina Mitic, Marianne Grafe, Petros Batsios and Irene Meyer

Cells 2022, 11(3), 407; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030407 - 25 Jan 2022

Cited by 5 | Viewed by 5382

Abstract

Dictyostelium cells undergo a semi-closed mitosis, during which the nuclear envelope (NE) persists; however, free diffusion between the cytoplasm and the nucleus takes place. To permit the formation of the mitotic spindle, the nuclear envelope must be permeabilized in order to allow diffusion [...] Read more.

Dictyostelium cells undergo a semi-closed mitosis, during which the nuclear envelope (NE) persists; however, free diffusion between the cytoplasm and the nucleus takes place. To permit the formation of the mitotic spindle, the nuclear envelope must be permeabilized in order to allow diffusion of tubulin dimers and spindle assembly factors into the nucleus. In Aspergillus, free diffusion of proteins between the cytoplasm and the nucleus is achieved by a partial disassembly of the nuclear pore complexes (NPCs) prior to spindle assembly. In order to determine whether this is also the case in Dictyostelium, we analysed components of the NPC by immunofluorescence microscopy and live cell imaging and studied their behaviour during interphase and mitosis. We observed that the NPCs are absent from the contact area of the nucleoli and that some nucleoporins also localize to the centrosome and the spindle poles. In addition, we could show that, during mitosis, the central FG protein NUP62, two inner ring components and Gle1 depart from the NPCs, while all other tested NUPs remained at the NE. This leads to the conclusion that indeed a partial disassembly of the NPCs takes place, which contributes to permeabilisation of the NE during semi-closed mitosis. Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

28 pages, 2045 KiB

Open AccessFeature PaperReview

The Nuclear Pore Complex: Birth, Life, and Death of a Cellular Behemoth

by Elisa Dultz, Matthias Wojtynek, Ohad Medalia and Evgeny Onischenko

Cells 2022, 11(9), 1456; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11091456 - 25 Apr 2022

Cited by 24 | Viewed by 7967

Abstract

Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500–1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of [...] Read more.

Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500–1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. There are a number of as yet unresolved questions about how the versatility of NPC assembly and composition is established, how cells monitor the functional state of NPCs or how they could be renewed. Here, we review current progress in our understanding of the key aspects of NPC architecture and lifecycle. Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

► Show Figures

Figure 1

19 pages, 1910 KiB

Open AccessReview

Generating Membrane Curvature at the Nuclear Pore: A Lipid Point of View

by Bas W. A. Peeters, Alexandra C. A. Piët and Maarten Fornerod

Cells 2022, 11(3), 469; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030469 - 29 Jan 2022

Cited by 16 | Viewed by 6044

Abstract

In addition to its structural role in enclosing and protecting the genome, the nuclear envelope (NE) forms a highly adaptive communication interface between the cytoplasm and the nuclear interior in eukaryotic cells. The double membrane of the NE is perforated by nuclear pores [...] Read more.

In addition to its structural role in enclosing and protecting the genome, the nuclear envelope (NE) forms a highly adaptive communication interface between the cytoplasm and the nuclear interior in eukaryotic cells. The double membrane of the NE is perforated by nuclear pores lined with large multi-protein structures, called nuclear-pore complexes (NPCs), which selectively allow the bi-directional transport of ions and macromolecular cargo. In order to nucleate a pore, the inner and outer nuclear membrane have to fuse at the site of NPC insertion, a process requiring both lipid bilayers to be deformed into highly curved structures. How this curvature is achieved and which factors are involved in inducing and stabilizing membrane curvature at the nuclear pore remain largely unclear. In this review, we will summarize the molecular mechanisms thought to be involved in membrane curvature generation, with a particular emphasis on the role of lipids and lipid metabolism in shaping the nuclear pore membrane. Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

► Show Figures

Figure 1

16 pages, 23002 KiB

Open AccessReview

Current Methods and Pipelines for Image-Based Quantitation of Nuclear Shape and Nuclear Envelope Abnormalities

by Anne F. J. Janssen, Sophia Y. Breusegem and Delphine Larrieu

Cells 2022, 11(3), 347; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030347 - 20 Jan 2022

Cited by 16 | Viewed by 8722

Abstract

Any given cell type has an associated “normal” nuclear morphology, which is important to maintain proper cellular functioning and safeguard genomic integrity. Deviations from this can be indicative of diseases such as cancer or premature aging syndrome. To accurately assess nuclear abnormalities, it [...] Read more.

Any given cell type has an associated “normal” nuclear morphology, which is important to maintain proper cellular functioning and safeguard genomic integrity. Deviations from this can be indicative of diseases such as cancer or premature aging syndrome. To accurately assess nuclear abnormalities, it is important to use quantitative measures of nuclear morphology. Here, we give an overview of several nuclear abnormalities, including micronuclei, nuclear envelope invaginations, blebs and ruptures, and review the current methods used for image-based quantification of these abnormalities. We discuss several parameters that can be used to quantify nuclear shape and compare their outputs using example images. In addition, we present new pipelines for quantitative analysis of nuclear blebs and invaginations. Quantitative analyses of nuclear aberrations and shape will be important in a wide range of applications, from assessments of cancer cell anomalies to studies of nucleus deformability under mechanical or other types of stress. Full article

(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Lipid and Protein Dynamics at the Nuclear Envelope

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI