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Cold Spring Harbor Symposia on... 2010In evolution, the nuclear envelope (NE) arose from the prokaryotic plasma membrane. NE-associated structures, such as nuclear pore complexes (NPCs), the nuclear lamina,... (Review)
Review
In evolution, the nuclear envelope (NE) arose from the prokaryotic plasma membrane. NE-associated structures, such as nuclear pore complexes (NPCs), the nuclear lamina, and nuclear envelope junctions (NEJs), have evolved to organize, among other things, chromatids within the three-dimensional space of the nucleus. NEJs represent patches of distinct integral membrane proteins of the outer and inner NE membranes, which, by interacting through conserved domains in the perinuclear space, closely align the two NE membranes. In a nuts-and-bolts configuration, the NEJs are linked to repetitive heterochromatin segments of chromatids on their nuclear side and to cytoskeletal elements on their cytoplasmic side. Cytoskeleton-generated mechanical forces are thereby effectively buffered to allow movement of nuclei in the viscous cytoplasm without disrupting the NE. Moreover, these same mechanical forces could generate distortions within the nucleus to facilitate chromatid fluctuations required for DNA repair, replication, and transcription. NPCs are the only route for bidirectional macromolecular transport between the cytoplasm and the nucleus. They also interact with euchromatin segments of chromatids. Thus far, crystallographic analyses of some nucleoporin contact sites suggest considerable plasticity. This flexibility has likely coevolved to not only buffer the mechanical forces propagated from the NEJs to the network of the more than 500 nucleoporins that make up a single NPC, but also impart fluctuations to NPC conformations for transporting large cargoes.
Topics: Animals; Chromatids; Lamins; Nuclear Envelope; Nuclear Lamina; Nuclear Pore; Nuclear Pore Complex Proteins
PubMed: 21047906
DOI: 10.1101/sqb.2010.75.004 -
Japanese Journal of Infectious Diseases 2015In this study, G proteins of the rabies virus (RABV) Kyoto strain were detected in the cytoplasm but not distributed at the cell membrane of mouse neuroblastoma (MNA)...
In this study, G proteins of the rabies virus (RABV) Kyoto strain were detected in the cytoplasm but not distributed at the cell membrane of mouse neuroblastoma (MNA) cells. G proteins of CVS-26 were detected in both the cell membrane and perinuclear space of MNA cells. We found that N-glycosylation of street RABV G protein by the insertion of the sequon Asn(204) induced the transfer of RABV G proteins to the cell surface membrane. Fixed RABV budding from the plasma membrane has been found to depend not only on G protein but also on other structural proteins such as M protein. However, the differing N-glycosylation of G protein could be associated with the distinct budding and antigenic features of RABV in street and fixed viruses. Our study of the association of N-glycan of G protein at Asn(204) with the transport of RABV G protein to the cell surface membrane contributes to the understanding of the evolution of fixed virus from street virus, which in turn would help for determine the mechanism underlying RABV budding and enhanced host immune responses.
Topics: Animals; Antigens, Viral; Asparagine; Fluorescent Antibody Technique, Indirect; Glycoproteins; Glycosylation; Humans; Mice; Protein Transport; Rabies; Tumor Cells, Cultured; Viral Envelope Proteins
PubMed: 25766612
DOI: 10.7883/yoken.JJID.2014.533 -
Journal of Cell Science Mar 2009Positioning the nucleus is essential for the formation of polarized cells, pronuclear migration, cell division, cell migration and the organization of specialized... (Review)
Review
Positioning the nucleus is essential for the formation of polarized cells, pronuclear migration, cell division, cell migration and the organization of specialized syncytia such as mammalian skeletal muscles. Proteins that are required for nuclear positioning also function during chromosome movement and pairing in meiosis. Defects in these processes lead to human diseases including laminopathies. To properly position the nucleus or move chromosomes within the nucleus, the cell must specify the outer surface of the nucleus and transfer forces across both membranes of the nuclear envelope. KASH proteins are specifically recruited to the outer nuclear membrane by SUN proteins, which reside in the inner nuclear membrane. KASH and SUN proteins physically interact in the perinuclear space, forming a bridge across the two membranes of the nuclear envelope. The divergent N-terminal domains of KASH proteins extend from the surface of the nucleus into the cytoplasm and interact with the cytoskeleton, whereas the N-termini of SUN proteins extend into the nucleoplasm to interact with the lamina or chromatin. The bridge of SUN and KASH across the nuclear envelope functions to transfer forces that are generated in the cytoplasm into the nucleoplasm during nuclear migration, nuclear anchorage, centrosome attachment, intermediate-filament association and telomere clustering.
Topics: Animals; Cell Line; Cell Nucleus; Chromosomes; Humans; Models, Biological; Nuclear Envelope; Nuclear Proteins
PubMed: 19225124
DOI: 10.1242/jcs.037622 -
Biochemical Society Transactions Dec 2011The mammalian NE (nuclear envelope), which separates the nucleus from the cytoplasm, is a complex structure composed of nuclear pore complexes, the outer and inner... (Review)
Review
The mammalian NE (nuclear envelope), which separates the nucleus from the cytoplasm, is a complex structure composed of nuclear pore complexes, the outer and inner nuclear membranes, the perinuclear space and the nuclear lamina (A- and B-type lamins). The NE is completely disassembled and reassembled at each cell division. In the present paper, we review recent advances in the understanding of the mechanisms implicated in the transport of inner nuclear membrane and nuclear lamina proteins from the endoplasmic reticulum to the nucleus in interphase cells and mitosis, with special attention to A-type lamins.
Topics: Animals; Humans; Lamin Type A; Membrane Proteins; Mitosis; Nuclear Envelope; Nuclear Proteins; Protein Transport
PubMed: 22103521
DOI: 10.1042/BST20110653 -
Plants (Basel, Switzerland) Feb 2022The response of chloroplasts to adverse environmental cues, principally increases in light intensity, stimulates chloroplast-to-nucleus retrograde signalling, which... (Review)
Review
The response of chloroplasts to adverse environmental cues, principally increases in light intensity, stimulates chloroplast-to-nucleus retrograde signalling, which leads to the induction of immediate protective responses and longer-term acclimation. Hydrogen peroxide (HO), generated during photosynthesis, is proposed to both initiate and transduce a retrograde signal in response to photoinhibitory light intensities. Signalling specificity achieved by chloroplast-sourced HO for signal transduction may be dependent upon the oft-observed close association of a proportion of these organelles with the nucleus. In this review, we consider more precisely the nature of the close association between a chloroplast appressed to the nucleus and the requirement for HO to cross both the double membranes of the chloroplast and nuclear envelopes. Of particular relevance is that the endoplasmic reticulum (ER) has close physical contact with chloroplasts and is contiguous with the nuclear envelope. Therefore, the perinuclear space, which transducing HO molecules would have to cross, may have an oxidising environment the same as the ER lumen. Based on studies in animal cells, the ER lumen may be a significant source of HO in plant cells arising from the oxidative folding of proteins. If this is the case, then there is potential for the ER lumen/perinuclear space to be an important location to modify chloroplast-to-nucleus HO signal transduction and thereby introduce modulation of it by additional different environmental cues. These would include for example, heat stress and pathogen infection, which induce the unfolded protein response characterised by an increased HO level in the ER lumen.
PubMed: 35214888
DOI: 10.3390/plants11040552 -
Cell Dec 2016In this issue of Cell, Skau et al. show that the formin FMN2 organizes a perinuclear actin cytoskeleton that protects the nucleus and its genomic content of migrating...
In this issue of Cell, Skau et al. show that the formin FMN2 organizes a perinuclear actin cytoskeleton that protects the nucleus and its genomic content of migrating cells squeezing through small spaces.
Topics: Actin Cytoskeleton; Actins; Cell Nucleus; Humans; Microfilament Proteins
PubMed: 27912053
DOI: 10.1016/j.cell.2016.11.024 -
Nagoya Journal of Medical Science Feb 2017A 65-year-old man was referred to our hospital for the treatment of a lesion on the medial lacrimal canthus of both eyes. He had a history of perinuclear anti-neutrophil...
A 65-year-old man was referred to our hospital for the treatment of a lesion on the medial lacrimal canthus of both eyes. He had a history of perinuclear anti-neutrophil cytoplasmic antibodies, i.e., pANCA-positive interstitial pneumonia. Orbital magnetic resonance imaging excluded space occupying lesions, and laboratory testing excluded thyroid-related diseases. The masses were excised, and histopathological examinations showed sebaceous gland hyperplasia and inflammatory changes around the gland. In addition, the specimen from the left eye showed a retention cyst possibly caused by an infection. It was also possible that the use of steroid was involved in the development of the lesions. A relationship between the ANCA and the lesions was not completely eliminated.
Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Humans; Inflammation; Lacrimal Apparatus Diseases; Lung Diseases, Interstitial; Male; Sebaceous Glands
PubMed: 28303065
DOI: 10.18999/nagjms.79.1.85 -
Journal of Virology Nov 2009Herpesviruses cross nuclear membranes (NMs) in two steps, as follows: (i) capsids assemble and bud through the inner NM into the perinuclear space, producing enveloped...
Herpesviruses cross nuclear membranes (NMs) in two steps, as follows: (i) capsids assemble and bud through the inner NM into the perinuclear space, producing enveloped virus particles, and (ii) the envelopes of these virus particles fuse with the outer NM. Two herpes simplex virus (HSV) glycoproteins, gB and gH (the latter, likely complexed as a heterodimer with gL), are necessary for the second step of this process. Mutants lacking both gB and gH accumulate in the perinuclear space or in herniations (membrane vesicles derived from the inner NM). Both gB and gH/gL are also known to act directly in fusing the virion envelope with host cell membranes during HSV entry into cells, i.e., both glycoproteins appear to function directly in different aspects of the membrane fusion process. We hypothesized that HSV gB and gH/gL also act directly in the membrane fusion that occurs during virus egress from the nucleus. Previous studies of the role of gB and gH/gL in nuclear egress involved HSV gB and gH null mutants that could potentially also possess gross defects in the virion envelope. Here, we produced recombinant HSV-expressing mutant forms of gB with single amino acid substitutions in the hydrophobic "fusion loops." These fusion loops are thought to play a direct role in membrane fusion by insertion into cellular membranes. HSV recombinants expressing gB with any one of four fusion loop mutations (W174R, W174Y, Y179K, and A261D) were unable to enter cells. Moreover, two of the mutants, W174Y and Y179K, displayed reduced abilities to mediate HSV cell-to-cell spread, and W174R and A261D exhibited no spread. All mutant viruses exhibited defects in nuclear egress, enveloped virions accumulated in herniations and in the perinuclear space, and fewer enveloped virions were detected on cell surfaces. These results support the hypothesis that gB functions directly to mediate the fusion between perinuclear virus particles and the outer NM.
Topics: Blotting, Western; Cell Line; DNA, Recombinant; Herpesvirus 1, Human; Humans; Nuclear Envelope; Viral Envelope Proteins; Viral Fusion Proteins; Virion; Virus Integration; Virus Internalization
PubMed: 19759132
DOI: 10.1128/JVI.01397-09 -
Biochimica Et Biophysica Acta Mar 1998Raf-1, A-Raf and B-Raf comprise a small family of highly conserved serine/threonine protein kinases, whose activities play a fundamental role in the control of...
Raf-1, A-Raf and B-Raf comprise a small family of highly conserved serine/threonine protein kinases, whose activities play a fundamental role in the control of proliferation and differentiation. The best studied family member, Raf-1, is expressed ubiquitously and constitutively, and its activity is regulated by post-translational mechanisms. Raf-1 can be activated by many signals that include growth factors, tumor promoters, inflammatory cytokines, calcium mobilization, DNA damaging agents, and oxygen radicals. Ras-mediated translocation of Raf-1 to the plasma membrane is a crucial step in its activation process, and is thought to facilitate phosphorylation by membrane-bound kinases. Raf-1 has also been reported to undergo intracellular redistribution following its activation: to the perinuclear space in murine NIH3T3 cells and rat hepatic Ito cells, and into the nucleus in gerbil hippocampal pyramidal cells and human MO7 leukemia cells. In contrast to the translocation to the plasma membrane, the perinuclear and/or nuclear translocation of Raf-1 has not been investigated in detail. In this paper, we report an examination of the subcellular localization of endogenous Raf-1 in a fibroblastic cell line (Rat-1) commonly used in transformation assays. Using the methods of cellular fractionation as well as in situ immunofluorescence, we show that no detectable movement of Raf-1 to the perinuclear or nuclear space can be observed. Tethering of activated Raf to the plasma membrane does not interfere with its transforming activity.
Topics: 3T3 Cells; Animals; Cell Line; Cell Nucleus; Cytoplasm; Fibroblasts; Fluorescent Antibody Technique; Gerbillinae; Hippocampus; Humans; Leukemia; Mice; Proto-Oncogene Proteins c-raf; Pyramidal Cells; RNA Processing, Post-Transcriptional; Rats; Recombinant Proteins; Subcellular Fractions; Transfection; Tumor Cells, Cultured
PubMed: 9551081
DOI: 10.1016/s0167-4889(97)00136-5 -
Cells Sep 2020Cell migration requires reposition and reshaping of the cell nucleus. The nuclear lamina is highly important for migration of both primary and cancer cells. B-type...
Cell migration requires reposition and reshaping of the cell nucleus. The nuclear lamina is highly important for migration of both primary and cancer cells. B-type lamins are important for proper migration of epicardial cells and neurons and increased lamin B to lamin A ratio accelerates cancer cell migration through confined spaces. Moreover, a positive association between lamin B1 levels and tumor formation and progression is found in various cancer types. Still, the molecular mechanism by which B-type lamins promote cell migration is not fully understood. To better understand this mechanism, we tested the effects of lamin B1 on perinuclear actin organization. Here we show that induction of melanoma cell migration leads to the formation of a cytosolic Linker of Nucleoskeleton and Cytoskeleton (LINC) complex-independent perinuclear actin rim, which has not been detected in migrating cells, yet. Significantly, increasing the levels of lamin B1 but not the levels of lamin A prevented perinuclear actin rim formation while accelerated the cellular migration rate. To interfere with the perinuclear actin rim, we generated a chimeric protein that is localized to the outer nuclear membrane and cleaves perinuclear actin filaments in a specific manner without disrupting other cytosolic actin filaments. Using this tool, we found that disruption of the perinuclear actin rim accelerated the cellular migration rate in a similar manner to lamin B1 over-expression. Taken together, our results suggest that increased lamin B1 levels can accelerate cell migration by inhibiting the association of the nuclear envelope with actin filaments that may reduce nuclear movement and deformability.
Topics: Actins; Cell Line, Tumor; Cell Movement; Cell Nucleus; Gelsolin; Humans; Lamin Type B; Melanoma
PubMed: 32987785
DOI: 10.3390/cells9102161