scholarly journals RASCAL Is a New Human Cytomegalovirus-Encoded Protein That Localizes to the Nuclear Lamina and in Cytoplasmic Vesicles at Late Times Postinfection

2010 ◽  
Vol 84 (13) ◽  
pp. 6483-6496 ◽  
Author(s):  
Matthew S. Miller ◽  
Wendy E. Furlong ◽  
Leesa Pennell ◽  
Marc Geadah ◽  
Laura Hertel
Keyword(s):  
Amino Acids ◽  
Nuclear Envelope ◽  
Human Cytomegalovirus ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Open Reading Frames ◽  
Short Version ◽  
Nuclear Egress ◽  
Cytoplasmic Vesicles ◽  
Associated Proteins

ABSTRACT The products of numerous open reading frames (ORFs) present in the genome of human cytomegalovirus (CMV) have not been characterized. Here, we describe the identification of a new CMV protein localizing to the nuclear envelope and in cytoplasmic vesicles at late times postinfection. Based on this distinctive localization pattern, we called this new protein nuclear r im- as sociated c ytomegalovir al protein, or RASCAL. Two RASCAL isoforms exist, a short version of 97 amino acids encoded by the majority of CMV strains and a longer version of 176 amino acids encoded by the Towne, Toledo, HAN20, and HAN38 strains. Both isoforms colocalize with lamin B in deep intranuclear invaginations of the inner nuclear membrane (INM) and in novel cytoplasmic vesicular structures possibly derived from the nuclear envelope. INM infoldings have been previously described as sites of nucleocapsid egress, which is mediated by the localized disruption of the nuclear lamina, promoted by the activities of viral and cellular kinases recruited by the lamina-associated proteins UL50 and UL53. RASCAL accumulation at the nuclear membrane required the presence of UL50 but not of UL53. RASCAL and UL50 also appeared to specifically interact, suggesting that RASCAL is a new component of the nuclear egress complex (NEC) and possibly involved in mediating nucleocapsid egress from the nucleus. Finally, the presence of RASCAL within cytoplasmic vesicles raises the intriguing possibility that this protein might participate in additional steps of virion maturation occurring after capsid release from the nucleus.

scholarly journals Nuclear envelope rupture: Actin fibers are putting the squeeze on the nucleus

2016 ◽  
Vol 215 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Jan Lammerding ◽  
Katarina Wolf
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Cell Biol ◽  
Biophysical Processes

Cells exhibit transient nuclear envelope ruptures during interphase, but the responsible biophysical processes remain unclear. In this issue, Hatch and Hetzer (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603053) show that actin fibers constrict the nucleus, causing chromatin protrusions and nuclear membrane ruptures at sites with nuclear lamina defects.

scholarly journals Nuclear envelope rupture is induced by actin-based nucleus confinement

2016 ◽  
Vol 215 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Emily M. Hatch ◽  
Martin W. Hetzer
Keyword(s):  
Nuclear Envelope ◽  
Cancer Cells ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Membrane Stability ◽  
Linc Complex ◽  
Actin Bundles ◽  
In Cells

Repeated rounds of nuclear envelope (NE) rupture and repair have been observed in laminopathy and cancer cells and result in intermittent loss of nucleus compartmentalization. Currently, the causes of NE rupture are unclear. Here, we show that NE rupture in cancer cells relies on the assembly of contractile actin bundles that interact with the nucleus via the linker of nucleoskeleton and cytoskeleton (LINC) complex. We found that the loss of actin bundles or the LINC complex did not rescue nuclear lamina defects, a previously identified determinant of nuclear membrane stability, but did decrease the number and size of chromatin hernias. Finally, NE rupture inhibition could be rescued in cells treated with actin-depolymerizing drugs by mechanically constraining nucleus height. These data suggest a model of NE rupture where weak membrane areas, caused by defects in lamina organization, rupture because of an increase in intranuclear pressure from actin-based nucleus confinement.

The nuclear envelope

2019 ◽  
pp. 140-146
Author(s):  
John C. Lucchesi
Keyword(s):  
Nuclear Envelope ◽  
Lipid Bilayers ◽  
Nuclear Membrane ◽  
Substantial Portion ◽  
Inner Membrane ◽  
Double Membrane ◽  
Stochastic Nature ◽  
Inner Surface ◽  
Associated Proteins ◽  
Or Gene

The nuclear envelope is a double membrane sheath made up of two lipid bilayers—an outer and an inner membrane. The inner surface of the inner membrane is associated with a meshwork of filaments made up of lamins and of lamin-associated proteins that constitute the lamina. A substantial portion of the genome contacts the lamina through lamina-associated domains (LADs). LADs usually position silent or gene-poor regions of the genome near the lamina and nuclear membrane. The position of some LADs is different in some cells of the same tissue, reflecting the stochastic nature of gene activity; it can also change during differentiation, allowing the necessary activation of particular genes. Contact of transcription units with nuclear pores can result in activation or, sometimes, repression. Some of the proteins that contribute to the structure of the pores can activate transcription by associating with genes or with super-enhancers away from the nuclear membrane.

scholarly journals Nuclear envelope organization in Dictyostelium discoideum

2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 509-519 ◽  
Author(s):  
Petros Batsios ◽  
Ralph Gräf ◽  
Michael P. Koonce ◽  
Denis A. Larochelle ◽  
Irene Meyer
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Major Constituent ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Linc Complex ◽  
Family Protein ◽  
Import And Export ◽  
Pore Complexes

The nuclear envelope consists of the outer and the inner nuclear membrane, the nuclear lamina and the nuclear pore complexes, which regulate nuclear import and export. The major constituent of the nuclear lamina of Dictyostelium is the lamin NE81. It can form filaments like B-type lamins and it interacts with Sun1, as well as with the LEM/HeH-family protein Src1. Sun1 and Src1 are nuclear envelope transmembrane proteins involved in the centrosome-nucleus connection and nuclear envelope stability at the nucleolar regions, respectively. In conjunction with a KASH-domain protein, Sun1 usually forms a so-called LINC complex. Two proteins with functions reminiscent of KASH-domain proteins at the outer nuclear membrane of Dictyostelium are known; interaptin which serves as an actin connector and the kinesin Kif9 which plays a role in the microtubule-centrosome connector. However, both of these lack the conserved KASH-domain. The link of the centrosome to the nuclear envelope is essential for the insertion of the centrosome into the nuclear envelope and the appropriate spindle formation. Moreover, centrosome insertion is involved in permeabilization of the mitotic nucleus, which ensures access of tubulin dimers and spindle assembly factors. Our recent progress in identifying key molecular players at the nuclear envelope of Dictyostelium promises further insights into the mechanisms of nuclear envelope dynamics.

scholarly journals Cytomegaloviral proteins that associate with the nuclear lamina: components of a postulated nuclear egress complex

2009 ◽  
Vol 90 (3) ◽  
pp. 579-590 ◽  
Author(s):  
Jens Milbradt ◽  
Sabrina Auerochs ◽  
Heinrich Sticht ◽  
Manfred Marschall
Keyword(s):  
Nuclear Envelope ◽  
Transmembrane Protein ◽  
Nuclear Lamina ◽  
Cellular Proteins ◽  
Lamin B ◽  
Nuclear Egress ◽  
Lamin B Receptor ◽  
Individual Interaction ◽  
Sequence Elements ◽  
Protein Recruitment

The nuclear egress of cytomegaloviral capsids traversing the nuclear envelope is dependent on a locally restricted destabilization of the rigid nuclear lamina. It has been suggested that the multi-component nuclear egress complex (NEC) that is formed is comprised of both viral and cellular proteins which act to recruit lamin-phosphorylating protein kinases. Recently, we reported that the lamina-associated human cytomegalovirus-encoded proteins pUL50 and pUL53, conserved among herpesviruses, interact with each other and recruit protein kinase C (PKC) to the nuclear envelope in transfected cells. The multiple interactions of the transmembrane protein pUL50 with pUL53, PKC and cellular PKC-binding protein p32, appear crucial to the formation of the NEC. In this study, we mapped individual interaction sequence elements of pUL50 by coimmunoprecipitation analysis of deletion mutants and yeast two-hybrid studies. Amino acids 1–250 were shown to be responsible for interaction with pUL53, 100–280 for PKC and 100–358 for p32. Interestingly, p32 specifically interacted with multiple NEC components, including the kinases PKC and pUL97, thus possibly acting as an adaptor for protein recruitment to the lamin B receptor. Notably, p32 was the only protein that interacted with the lamin B receptor. Immunofluorescence studies visualized the colocalization of NEC components at the nuclear rim in coexpression studies. The data imply that a tight interaction between at least six viral and cellular proteins leads to the formation of a postulated multi-protein complex required for nuclear egress.

scholarly journals SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors

2015 ◽  
Vol 26 (10) ◽  
pp. 1918-1934 ◽  
Author(s):  
Sergio A. Mojica ◽  
Kelley M. Hovis ◽  
Matthew B. Frieman ◽  
Bao Tran ◽  
Ru-ching Hsia ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Chlamydia Psittaci ◽  
Hek293 Cells ◽  
Secreted Protein ◽  
Inner Nuclear Membrane ◽  
Type Iii ◽  
Infected Cells ◽  
Digitonin Permeabilization

SINC, a new type III secreted protein of the avian and human pathogen Chlamydia psittaci, uniquely targets the nuclear envelope of C. psittaci–infected cells and uninfected neighboring cells. Digitonin-permeabilization studies of SINC-GFP–transfected HeLa cells indicate that SINC targets the inner nuclear membrane. SINC localization at the nuclear envelope was blocked by importazole, confirming SINC import into the nucleus. Candidate partners were identified by proximity to biotin ligase-fused SINC in HEK293 cells and mass spectrometry (BioID). This strategy identified 22 candidates with high confidence, including the nucleoporin ELYS, lamin B1, and four proteins (emerin, MAN1, LAP1, and LBR) of the inner nuclear membrane, suggesting that SINC interacts with host proteins that control nuclear structure, signaling, chromatin organization, and gene silencing. GFP-SINC association with the native LEM-domain protein emerin, a conserved component of nuclear “lamina” structure, or with a complex containing emerin was confirmed by GFP pull down. Our findings identify SINC as a novel bacterial protein that targets the nuclear envelope with the capability of globally altering nuclear envelope functions in the infected host cell and neighboring uninfected cells. These properties may contribute to the aggressive virulence of C. psittaci.

scholarly journals Novel Mode of Phosphorylation-triggered Reorganization of the Nuclear Lamina during Nuclear Egress of Human Cytomegalovirus

2010 ◽  
Vol 285 (18) ◽  
pp. 13979-13989 ◽  
Author(s):  
Jens Milbradt ◽  
Rike Webel ◽  
Sabrina Auerochs ◽  
Heinrich Sticht ◽  
Manfred Marschall
Keyword(s):  
Human Cytomegalovirus ◽  
Nuclear Lamina ◽  
Nuclear Egress

scholarly journals Decreased torsinA or LINC Complex Function Rescues a Laminopathy in Caenorhabditis elegans

2020 ◽  
Author(s):  
Gabriela Huelgas-Morales ◽  
Mark Sanders ◽  
Gemechu Mekonnen ◽  
Tatsuya Tsukamoto ◽  
David Greenstein
Keyword(s):  
Nuclear Envelope ◽  
Complex Function ◽  
Nuclear Lamina ◽  
Premature Aging ◽  
Linc Complex ◽  
Force Transmission ◽  
Complex Activity ◽  
Aaa Atpase ◽  
C Elegans ◽  
Associated Proteins

AbstractThe function of the nucleus depends on the integrity of the nuclear lamina, an intermediate filament network associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex spanning the nuclear envelope. In turn, the AAA+ ATPase torsinA regulates force transmission from the cytoskeleton to the nucleus. In humans, mutations affecting nuclear envelope-associated proteins cause laminopathies, including progeria, myopathy, and dystonia. We report that decreasing the function of the C. elegans torsinA homolog, OOC-5, rescues the sterility and premature aging caused by a null mutation in the single worm lamin homolog, lmn-1. Loss of OOC-5 activity prevents nuclear collapse in lmn-1 mutants by disrupting the function of the LINC complex. These results suggest that LINC complex-transmitted forces damage nuclei with a compromised nuclear lamina.One Sentence SummaryInhibiting LINC complex activity prevents a progeric syndrome in C. elegans.

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