Intranuclear membranes induced by lipidated proteins are derived from the nuclear envelope

Linde, Nina F.; Stick, Reimer

doi:10.4161/nucl.1.4.12352

Cited by 13 publications

(8 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cryo-EM of these filaments revealed paracrystals and filaments composed of three to four protofilaments [54], confirming the feSEM data (see above) that already indicated thinner filaments with accordingly fewer protofilaments [47]. In in vitro experiments, in the presence of calcium, lamins showed a tendency to form large paracrystalline arrays with many filaments present and a thickness of ~100 nm [39]. The capacity of forming such large paracrystals may also depend on the presence of the C-terminal Ig-fold within the LTD present in most lamins [45,52].…”

Section: Discussionsupporting

confidence: 64%

“…Previous work proved the Xenopus oocyte expression system as a valuable tool to display lamin assemblies at the inner surface of the nuclear envelope, as the latter can be manually dissected and separated from chromatin, which is not tightly attached to the NE in these cells [38]. Here, expression of lipidated nuclear proteins carrying a CaaX-box such as lamins results in formation of intranuclear membrane stacks [31,39]. These membrane stacks turned out to be useful to analyze lamin filaments other than Xenopus lamin LIII [31].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Supramolecular Structures of the Dictyostelium Lamin NE81

Grafe

Batsios

Meyer

et al. 2019

Cells

View full text Add to dashboard Cite

Nuclear lamins are nucleus-specific intermediate filaments (IF) found at the inner nuclear membrane (INM) of the nuclear envelope (NE). Together with nuclear envelope transmembrane proteins, they form the nuclear lamina and are crucial for gene regulation and mechanical robustness of the nucleus and the whole cell. Recently, we characterized Dictyostelium NE81 as an evolutionarily conserved lamin-like protein, both on the sequence and functional level. Here, we show on the structural level that the Dictyostelium NE81 is also capable of assembling into filaments, just as metazoan lamin filament assemblies. Using field-emission scanning electron microscopy, we show that NE81 expressed in Xenopous oocytes forms filamentous structures with an overall appearance highly reminiscent of Xenopus lamin B2. The in vitro assembly properties of recombinant His-tagged NE81 purified from Dictyostelium extracts are very similar to those of metazoan lamins. Super-resolution stimulated emission depletion (STED) and expansion microscopy (ExM), as well as transmission electron microscopy of negatively stained purified NE81, demonstrated its capability of forming filamentous structures under low-ionic-strength conditions. These results recommend Dictyostelium as a non-mammalian model organism with a well-characterized nuclear envelope involving all relevant protein components known in animal cells.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Supramolecular Structures of the Dictyostelium Lamin NE81

Grafe

Batsios

Meyer

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…Type I NR are finger-like expansions into nucleoplasm of the INM only, whereas type II NR involves the invagination of both INM and ONM, including a portion of cytosol and sometimes cell organelles. NR development can be induced by increasing the amount of isoprenylated nuclear proteins [80][81][82][83][84], and was also observed in genetic diseases resulting from prelamin A processing defects [85] (Fig. 1C).…”

Section: Nuclear Localization Of Lamins Ne and Nucleoplasmic Reticulmentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features associated to progeria. New therapeutic strategies under study, in particular targeting the protein expression pathway at the mRNA level, have shown a remarkable efficacy both in vitro in cells and in vivo in mice models. Strategies intending to clear the toxic accumulated proteins from the nucleus are also under evaluation. However, although exceedingly rare, improving our knowledge of genetic progeroid syndromes and searching for innovative and efficient therapies in these syndromes is of paramount importance as, even before they can be used to save lives, they may significantly (i) expand the affected childrens' lifespan and preserve their quality of life; (ii) improve our understanding of aging-related disorders and other more common diseases; and (iii) expand our fundamental knowledge of physiological aging and its links with major physiological processes such as those involved in oncogenesis.

show abstract

“…Evident in the literature are also reports that demonstrate examples of cellular INM proteins that display this activity when overexpressed. This has been established for lamins and other nuclear membrane-associated proteins (55). Overexpression of these proteins results in formation of intranuclear membrane arrays, and this activity can be transferred to GFP by the incorporation of an NLS and the CaaX motif from N-ras (56).…”

Section: Discussionmentioning

confidence: 99%

Interactions of the Kaposi's Sarcoma-Associated Herpesvirus Nuclear Egress Complex: ORF69 Is a Potent Factor for Remodeling Cellular Membranes

Luitweiler

Henson

Pryce

et al. 2013

J Virol

View full text Add to dashboard Cite

All herpesviruses encode a complex of two proteins, referred to as the nuclear egress complex (NEC), which together facilitate the exit of assembled capsids from the nucleus. Previously, we showed that the Kaposi's sarcoma-associated herpesvirus (KSHV) NEC specified by the ORF67 and ORF69 genes when expressed in insect cells using baculoviruses for protein expression forms a complex at the nuclear membrane and remodels these membranes to generate nuclear membrane-derived vesicles. In this study, we have analyzed the functional domains of the KSHV NEC proteins and their interactions. Site-directed mutagenesis of gammaherpesvirus conserved residues revealed functional domains of these two proteins, which in many cases abolish the formation of the NEC and remodeling of nuclear membranes. Small in-frame deletions within ORF67 in all cases result in loss of the ability of the mutant protein to induce cellular membrane proliferation as well as to interact with ORF69. Truncation of the C terminus of ORF67 that resides in the perinuclear space does not impair the functions of ORF67; however, deletion of the transmembrane domain of ORF67 produces a protein that cannot induce membrane proliferation but can still interact with ORF69 in the nucleus and can be tethered to the nuclear membrane by virtue of its interaction with the wild-type-membrane-anchored ORF67. In-frame deletions in ORF69 have varied effects on NEC formation, but all abolish remodeling of nuclear membranes into circular structures. One mutant interacts with ORF67 as well as the wild-type protein but cannot function in membrane curvature and fission events that generate circular vesicles. These studies genetically confirm that ORF67 is required for cellular membrane proliferation and that ORF69 is the factor required to remodel these duplicated membranes into circular-virion-size vesicles. Furthermore, we also investigated the NEC encoded by Epstein-Barr virus (EBV). The EBV complex comprised of BFRF1 and BFLF2 was visualized at the nuclear membrane using autofluorescent protein fusions. BFRF1 is a potent inducer of membrane proliferation; however, BFLF2 cannot remodel these membranes into circular structures. What was evident is the superior remodeling activity of ORF69, which could convert the host membrane proliferations induced by BFRF1 into circular structures.

show abstract

Intranuclear membranes induced by lipidated proteins are derived from the nuclear envelope

Cited by 13 publications

References 58 publications

Supramolecular Structures of the Dictyostelium Lamin NE81

Supramolecular Structures of the Dictyostelium Lamin NE81

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Interactions of the Kaposi's Sarcoma-Associated Herpesvirus Nuclear Egress Complex: ORF69 Is a Potent Factor for Remodeling Cellular Membranes

Contact Info

Product

Resources

About