scholarly journals Access of torsinA to the inner nuclear membrane is activity dependent and regulated in the endoplasmic reticulum

2015 ◽  
Vol 128 (15) ◽  
pp. 2854-2865 ◽  
Author(s):  
R. E. Goodchild ◽  
A. L. Buchwalter ◽  
T. V. Naismith ◽  
K. Holbrook ◽  
K. Billion ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Nuclear Membrane ◽  
Inner Nuclear Membrane ◽  
Activity Dependent

scholarly journals The fates of chicken nuclear lamin proteins during mitosis: evidence for a reversible redistribution of lamin B2 between inner nuclear membrane and elements of the endoplasmic reticulum.

1988 ◽  
Vol 107 (2) ◽  
pp. 397-406 ◽  
Author(s):  
R Stick ◽  
B Angres ◽  
C F Lehner ◽  
E A Nigg
Keyword(s):  
Endoplasmic Reticulum ◽  
Nuclear Membrane ◽  
Membrane Vesicles ◽  
Soluble Form ◽  
Lamin A ◽  
Cell Fractionation ◽  
Lamin B ◽  
Inner Nuclear Membrane ◽  
Nuclear Lamin ◽  
Mitotic Cells

In chicken, three structurally distinct nuclear lamin proteins have been described. According to their migration on two-dimensional gels, these proteins have been designated as lamins A, B1, and B2. To investigate the functional relationship between chicken lamins and their mammalian counterparts, we have examined here the state of individual chicken lamin proteins during mitosis. Current models proposing functional specializations of mammalian lamin subtypes are in fact largely based on the observation that during mitosis mammalian lamin B remains associated with membrane vesicles, whereas lamins A and C become freely soluble. Cell fractionation experiments combined with immunoblotting show that during mitosis both chicken lamins B1 and B2 remain associated with membranes, whereas lamin A exists in a soluble form. In situ immunoelectron microscopy carried out on mitotic cells also reveals membrane association of lamin B2, whereas the distribution of lamin A is random. From these results we conclude that both chicken lamins B1 and B2 may functionally resemble mammalian lamin B. Interestingly, immunolabeling of mitotic cells revealed an association of lamin B2 with extended membrane cisternae that resembled elements of the endoplasmic reticulum. Quantitatively, we found that all large endoplasmic reticulum-like membranes present in metaphase cells were decorated with lamin B2-specific antibodies. Given that labeling of these mitotic membranes was lower than labeling of interphase nuclear envelopes, it appears likely that during mitotic disassembly and reassembly of the nuclear envelope lamin B2 may reversibly distribute between the inner nuclear membrane and the endoplasmic reticulum.

scholarly journals Activation of endoplasmic reticulum stress via clustering of inner nuclear membrane proteins

2021 ◽  
Author(s):  
Sandra Vidak ◽  
Leonid A. Serebryannyy ◽  
Tom Misteli
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Nuclear Membrane ◽  
Premature Aging ◽  
Cellular Mechanisms ◽  
Inner Nuclear Membrane ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Hutchinson Gilford Progeria Syndrome

One of the major cellular mechanisms to ensure protein homeostasis is the endoplasmic reticulum (ER) stress response. This pathway is typically triggered by accumulation of misfolded proteins in the ER lumen. Here we describe activation of ER stress via protein aggregation in the cell nucleus. We find in the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) activation of ER stress due to the aggregation of the diseases-causing progerin protein at the nuclear envelope. The presence of nucleoplasmic protein aggregates is sensed and signaled to the ER lumen via immobilization and clustering of the inner nuclear membrane protein SUN2, leading to activation of the Unfolded Protein Response (UPR). These results identify a nuclear trigger of ER stress and they provide insight into the molecular disease mechanisms of HGPS.

scholarly journals Targeting of LRRC59 to the Endoplasmic Reticulum and the Inner Nuclear Membrane

2019 ◽  
Vol 20 (2) ◽  
pp. 334 ◽  
Author(s):  
Marina Blenski ◽  
Ralph Kehlenbach
Keyword(s):  
Endoplasmic Reticulum ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Import ◽  
Transmembrane Domain ◽  
Membrane Insertion ◽  
Leucine Rich Repeat ◽  
Inner Nuclear Membrane ◽  
Importin Α ◽  
Major Route

LRRC59 (leucine-rich repeat-containing protein 59) is a tail-anchored protein with a single transmembrane domain close to its C-terminal end that localizes to the endoplasmic reticulum (ER) and the nuclear envelope. Here, we investigate the mechanisms of membrane integration of LRRC59 and its targeting to the inner nuclear membrane (INM). Using purified microsomes, we show that LRRC59 can be post-translationally inserted into ER-derived membranes. The TRC-pathway, a major route for post-translational membrane insertion, is not required for LRRC59. Like emerin, another tail-anchored protein, LRRC59 reaches the INM, as demonstrated by rapamycin-dependent dimerization assays. Using different approaches to inhibit importin α/β-dependent nuclear import of soluble proteins, we show that the classic nuclear transport machinery does not play a major role in INM-targeting of LRRC59. Instead, the size of the cytoplasmic domain of LRRC59 is an important feature, suggesting that targeting is governed by passive diffusion.

scholarly journals Probing the Environment of Emerin by Enhanced Ascorbate Peroxidase 2 (APEX2)-Mediated Proximity Labeling

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 605 ◽  
Author(s):  
Marret Müller ◽  
Christina James ◽  
Christof Lenz ◽  
Henning Urlaub ◽  
Ralph H. Kehlenbach
Keyword(s):  
Mass Spectrometry ◽  
Endoplasmic Reticulum ◽  
Ascorbate Peroxidase ◽  
Nuclear Membrane ◽  
Standard Approach ◽  
Lamin A ◽  
Inner Nuclear Membrane ◽  
Close Proximity ◽  
Interaction Partners ◽  
Genetic Fusion

Emerin is one of the best characterized proteins of the inner nuclear membrane, but can also occur at the level of the endoplasmic reticulum. We now use enhanced ascorbate peroxidase 2 (APEX2) to probe the environment of emerin. APEX2 can be used as a genetic tag that produces short-lived yet highly reactive biotin species, allowing the modification of proteins that interact with or are in very close proximity to the tagged protein. Biotinylated proteins can be isolated using immobilized streptavidin and analyzed by mass spectrometry. As an alternative to the standard approach with a genetic fusion of APEX2 to emerin, we also used RAPIDS (rapamycin- and APEX-dependent identification of proteins by SILAC), a method with improved specificity, where the peroxidase interacts with the protein of interest (i.e., emerin) only upon addition of rapamycin to the cells. We compare these different approaches, which, together, identify well-known interaction partners of emerin like lamin A and the lamina associated polypeptide 1 (LAP1), as well as novel proximity partners.

scholarly journals System analysis shows distinct mechanisms and common principles of nuclear envelope protein dynamics

2011 ◽  
Vol 193 (1) ◽  
pp. 109-123 ◽  
Author(s):  
Nikolaj Zuleger ◽  
David A. Kelly ◽  
A. Christine Richardson ◽  
Alastair R. W. Kerr ◽  
Martin W. Goldberg ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
System Analysis ◽  
Nuclear Pore ◽  
Binding Affinities ◽  
Inner Nuclear Membrane ◽  
Wide Range ◽  
Recovery Times

The nuclear envelope contains >100 transmembrane proteins that continuously exchange with the endoplasmic reticulum and move within the nuclear membranes. To better understand the organization and dynamics of this system, we compared the trafficking of 15 integral nuclear envelope proteins using FRAP. A surprising 30-fold range of mobilities was observed. The dynamic behavior of several of these proteins was also analyzed after depletion of ATP and/or Ran, two functions implicated in endoplasmic reticulum–inner nuclear membrane translocation. This revealed that ATP- and Ran-dependent translocation mechanisms are distinct and not used by all inner nuclear membrane proteins. The Ran-dependent mechanism requires the phenylalanine-glycine (FG)-nucleoporin Nup35, which is consistent with use of the nuclear pore complex peripheral channels. Intriguingly, the addition of FGs to membrane proteins reduces FRAP recovery times, and this also depends on Nup35. Modeling of three proteins that were unaffected by either ATP or Ran depletion indicates that the wide range in mobilities could be explained by differences in binding affinities in the inner nuclear membrane.

Lamin B receptor: role on chromatin structure, cellular senescence and possibly aging

2020 ◽  
Vol 477 (14) ◽  
pp. 2715-2720
Author(s):  
Susana Castro-Obregón
Keyword(s):  
Cellular Senescence ◽  
Nuclear Membrane ◽  
Chromatin Structure ◽  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Chimeric Protein ◽  
Nuclear Lamina ◽  
Lamin B ◽  
Inner Nuclear Membrane ◽  
Lamin B Receptor

The nuclear envelope is composed by an outer nuclear membrane and an inner nuclear membrane, which is underlain by the nuclear lamina that provides the nucleus with mechanical strength for maintaining structure and regulates chromatin organization for modulating gene expression and silencing. A layer of heterochromatin is beneath the nuclear lamina, attached by inner nuclear membrane integral proteins such as Lamin B receptor (LBR). LBR is a chimeric protein, having also a sterol reductase activity with which it contributes to cholesterol synthesis. Lukasova et al. showed that when DNA is damaged by ɣ-radiation in cancer cells, LBR is lost causing chromatin structure changes and promoting cellular senescence. Cellular senescence is characterized by terminal cell cycle arrest and the expression and secretion of various growth factors, cytokines, metalloproteinases, etc., collectively known as senescence-associated secretory phenotype (SASP) that cause chronic inflammation and tumor progression when they persist in the tissue. Therefore, it is fundamental to understand the molecular basis for senescence establishment, maintenance and the regulation of SASP. The work of Lukasova et al. contributed to our understanding of cellular senescence establishment and provided the basis that lead to the further discovery that chromatin changes caused by LBR reduction induce an up-regulated expression of SASP factors. LBR dysfunction has relevance in several diseases and possibly in physiological aging. The potential bifunctional role of LBR on cellular senescence establishment, namely its role in chromatin structure together with its enzymatic activity contributing to cholesterol synthesis, provide a new target to develop potential anti-aging therapies.

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