scholarly journals An integral protein of the inner nuclear membrane localizes to the mitotic spindle in mammalian cells

2009 ◽  
Vol 122 (12) ◽  
pp. 2100-2107 ◽  
Author(s):  
C. Buch ◽  
R. Lindberg ◽  
R. Figueroa ◽  
S. Gudise ◽  
E. Onischenko ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Mitotic Spindle ◽  
Mammalian Cells ◽  
Inner Nuclear Membrane ◽  
Integral Protein

scholarly journals A transmembrane inner nuclear membrane protein in the mitotic spindle

Nucleus ◽  
2010 ◽  
Vol 1 (3) ◽  
pp. 249-253 ◽  
Author(s):  
Ricardo Figueroa ◽  
Santhosh Gudise ◽  
Veronica Larsson ◽  
Einar Hallberg
Keyword(s):  
Membrane Protein ◽  
Nuclear Membrane ◽  
Mitotic Spindle ◽  
Inner Nuclear Membrane ◽  
Inner Nuclear Membrane Protein ◽  
Nuclear Membrane Protein

scholarly journals Signals and structural features involved in integral membrane protein targeting to the inner nuclear membrane.

1995 ◽  
Vol 130 (1) ◽  
pp. 15-27 ◽  
Author(s):  
B Soullam ◽  
H J Worman
Keyword(s):  
Membrane Protein ◽  
Nuclear Membrane ◽  
Structural Features ◽  
Inner Nuclear Membrane ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Integral Protein ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal ◽  
Amino Terminal Domain

We have examined transfected cells by immunofluorescence microscopy to determine the signals and structural features required for the targeting of integral membrane proteins to the inner nuclear membrane. Lamin B receptor (LBR) is a resident protein of the nuclear envelope inner membrane that has a nucleoplasmic, amino-terminal domain and a carboxyl-terminal domain with eight putative transmembrane segments. The amino-terminal domain of LBR can target both a cytosolic protein to the nucleus and a type II integral protein to the inner nuclear membrane. Neither a nuclear localization signal (NLS) of a soluble protein, nor full-length histone H1, can target an integral protein to the inner nuclear membrane although they can target cytosolic proteins to the nucleus. The addition of an NLS to a protein normally located in the inner nuclear membrane, however, does not inhibit its targeting. When the amino-terminal domain of LBR is increased in size from approximately 22.5 to approximately 70 kD, the chimeric protein cannot reach the inner nuclear membrane. The carboxyl-terminal domain of LBR, separated from the amino-terminal domain, also concentrates in the inner nuclear membrane, demonstrating two nonoverlapping targeting signals in this protein. Signals and structural features required for the inner nuclear membrane targeting of proteins are distinct from those involved in targeting soluble polypeptides to the nucleoplasm. The structure of the nucleocytoplasmic domain of an inner nuclear membrane protein also influences targeting, possibly because of size constraints dictated by the lateral channels of the nuclear pore complexes.

scholarly journals Loss of a-Type Lamin Expression Compromises Nuclear Envelope Integrity Leading to Muscular Dystrophy

1999 ◽  
Vol 147 (5) ◽  
pp. 913-920 ◽  
Author(s):  
Teresa Sullivan ◽  
Diana Escalante-Alcalde ◽  
Harshida Bhatt ◽  
Miriam Anver ◽  
Narayan Bhat ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Mammalian Cells ◽  
Nuclear Architecture ◽  
Nuclear Lamina ◽  
Postnatal Growth ◽  
Developmentally Regulated ◽  
Inner Nuclear Membrane ◽  
Cardiac Muscles

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD.

scholarly journals Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress

2019 ◽  
Author(s):  
Abigail Buchwalter ◽  
Roberta Schulte ◽  
Hsiao Tsai ◽  
Juliana Capitanio ◽  
Martin Hetzer
Keyword(s):  
Er Stress ◽  
Nuclear Membrane ◽  
Mammalian Cells ◽  
Vesicular Transport ◽  
Vesicular Trafficking ◽  
Nuclear Pore ◽  
Inner Nuclear Membrane ◽  
Turn Over ◽  
Inner Nuclear Membrane Protein

AbstractThe inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.

scholarly journals A transmembrane inner nuclear membrane protein in the mitotic spindle

Nucleus ◽  
2010 ◽  
Vol 1 (3) ◽  
pp. 249-253 ◽  
Author(s):  
Ricardo Figueroa ◽  
Santhosh Gudise ◽  
Veronica Larsson ◽  
Einar Hallberg
Keyword(s):  
Membrane Protein ◽  
Nuclear Membrane ◽  
Mitotic Spindle ◽  
Inner Nuclear Membrane ◽  
Inner Nuclear Membrane Protein ◽  
Nuclear Membrane Protein

scholarly journals Live imaging and modeling of inner nuclear membrane targeting reveals its molecular requirements in mammalian cells

2015 ◽  
Vol 209 (5) ◽  
pp. 705-720 ◽  
Author(s):  
Andrea Boni ◽  
Antonio Z. Politi ◽  
Petr Strnad ◽  
Wanqing Xiang ◽  
M. Julius Hossain ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Mammalian Cells ◽  
Protein Transport ◽  
Nuclear Architecture ◽  
Functional Requirements ◽  
Retention Model ◽  
Inner Nuclear Membrane ◽  
Nuclear Lamins ◽  
Lamin B Receptor ◽  
And Function

Targeting of inner nuclear membrane (INM) proteins is essential for nuclear architecture and function, yet its mechanism remains poorly understood. Here, we established a new reporter that allows real-time imaging of membrane protein transport from the ER to the INM using Lamin B receptor and Lap2β as model INM proteins. These reporters allowed us to characterize the kinetics of INM targeting and establish a mathematical model of this process and enabled us to probe its molecular requirements in an RNA interference screen of 96 candidate genes. Modeling of the phenotypes of genes involved in transport of these INM proteins predicted that it critically depended on the number and permeability of nuclear pores and the availability of nuclear binding sites, but was unaffected by depletion of most transport receptors. These predictions were confirmed with targeted validation experiments on the functional requirements of nucleoporins and nuclear lamins. Collectively, our data support a diffusion retention model of INM protein transport in mammalian cells.

Nuclear envelope breakdown in mammalian cells involves stepwise lamina disassembly and microtubule-drive deformation of the nuclear membrane

1997 ◽  
Vol 110 (17) ◽  
pp. 2129-2140 ◽  
Author(s):  
S.D. Georgatos ◽  
A. Pyrpasopoulou ◽  
P.A. Theodoropoulos
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Mitotic Spindle ◽  
Mammalian Cells ◽  
Nuclear Lamina ◽  
Early Prophase ◽  
Nuclear Surface ◽  
Late Prophase ◽  
Lamin B ◽  
Nuclear Envelope Breakdown

We have studied nuclear envelope disassembly in mammalian cells by morphological methods. The first signs of nuclear lamina depolymerization become evident in early prophase as A-type lamins start dissociating from the nuclear lamina and diffuse into the nucleoplasm. While B-type lamins are still associated with the inner nuclear membrane, two symmetrical indentations develop on antidiametric sites of the nuclear envelope. These indentations accommodate the sister centrosomes and associated astral microtubules. At mid- to late prophase, elongating microtubules apparently push on the nuclear surface and eventually penetrate the nucleus. At this point the nuclear envelope becomes freely permeable to large ligands, as indicated by experiments with digitonin-treated cells and by the massive release of solubilized A-type lamins into the cytoplasm. At the prophase/prometaphase transition, the B-type lamina is fragmented, but ‘islands’ of lamin B polymer can still be discerned on the tips of congressing chromosomes. Finally, at metaphase, the lamin B polymer breaks down into small pieces, which tend to concentrate in the area of the mitotic spindle. Nuclear envelope breakdown is not prevented when the microtubules are depolymerized by nocodazole; however, the mode of nuclear lamina fragmentation in the absence of microtubules is markedly different from the normal one and involves multiple raffles and gaps, which develop rapidly along the entire surface of the nuclear envelope. These data suggest that nuclear envelope disassembly is a stepwise process in which the microtubules play an important part.

scholarly journals Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Abigail Buchwalter ◽  
Roberta Schulte ◽  
Hsiao Tsai ◽  
Juliana Capitanio ◽  
Martin Hetzer
Keyword(s):  
Er Stress ◽  
Nuclear Membrane ◽  
Mammalian Cells ◽  
Vesicular Transport ◽  
Vesicular Trafficking ◽  
Nuclear Pore ◽  
Inner Nuclear Membrane ◽  
Turn Over ◽  
Inner Nuclear Membrane Protein

The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.

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