scholarly journals FG repeats facilitate integral protein trafficking to the inner nuclear membrane

2011 ◽  
Vol 4 (5) ◽  
pp. 557-559 ◽  
Author(s):  
Alastair R. W. Kerr ◽  
Eric C. Schirmer
Keyword(s):  
Nuclear Membrane ◽  
Protein Trafficking ◽  
Inner Nuclear Membrane ◽  
Integral 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 Baculovirus Data Suggest a Common but Multifaceted Pathway for Sorting Proteins to the Inner Nuclear Membrane

2008 ◽  
Vol 83 (3) ◽  
pp. 1280-1288 ◽  
Author(s):  
Sharon C. Braunagel ◽  
Virginia Cox ◽  
Max D. Summers
Keyword(s):  
Viral Infection ◽  
Nuclear Membrane ◽  
Protein Trafficking ◽  
Protein Translocation ◽  
Protein Markers ◽  
Inner Nuclear Membrane ◽  
Dynamic Relationship ◽  
Importin Α ◽  
In Transit ◽  
Er Membrane

ABSTRACT Multiple unique protein markers sorted to the inner nuclear membrane (INM) from the Autographa californica nucleopolyhedrovirus occlusion-derived virus (ODV) envelope were used to decipher common elements of the sorting pathway of integral membrane proteins from their site of insertion into the membrane of the endoplasmic reticulum (ER) through their transit to the INM. The data show that during viral infection, the viral protein FP25K is a partner for all known ODV envelope proteins and that BV/ODV-E26 (designated E26) is a partner for some, but not all, such proteins. The association with the ER membrane of FP25K, E26, and the cellular INM-sorting protein importin-α-16 is not static; rather, these sorting proteins are actively recruited to the ER membrane based upon requirements of the proteins in transit to the INM. Colocalization analysis using an ODV envelope protein and importin-α-16 shows that during viral infection, importin-α-16 translocates across the pore membrane to the INM and then is incorporated into the virus-induced intranuclear membranes. Thus, the association of importin-α-16 and INM-directed proteins appears to remain at least through protein translocation across the pore membrane to the INM. Overall, the data suggest that multiple levels of regulation facilitate INM-directed protein trafficking, and that proteins participating in this sorting pathway have a dynamic relationship with each other and the membrane of the ER.

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

Intracellular trafficking of MAN1, an integral protein of the nuclear envelope inner membrane

2002 ◽  
Vol 115 (7) ◽  
pp. 1361-1371 ◽  
Author(s):  
Wei Wu ◽  
Feng Lin ◽  
Howard J. Worman
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Fluorescent Protein ◽  
Subcellular Location ◽  
Globular Domain ◽  
Retention Model ◽  
Inner Nuclear Membrane ◽  
Terminal Domain ◽  
Integral Protein ◽  
Green Fluorescent

MAN1 is an integral protein of the inner nuclear membrane that shares the LEM domain, a conserved globular domain of approximately 40 amino acids, with lamina-associated polypeptide (LAP) 2 and emerin. Confocal immuofluorescence microscopy studies of the intracellular targeting of truncated forms of MAN1 showed that the nucleoplasmic, N-terminal domain is necessary for inner nuclear membrane retention. A protein containing the N-terminal domain with the first transmembrane segment of MAN1 is retained in the inner nuclear membrane, whereas the transmembrane segments with the C-terminal domain of MAN1 is not targeted to the inner nuclear membrane. The N-terminal domain of MAN1 is also sufficient for inner nuclear membrane targeting as it can target a chimeric type II integral protein to this subcellular location. Deletion mutants of the N-terminal of MAN1 are not efficiently retained in the inner nuclear membrane. When the N-terminal domain of MAN1 is increased in size from∼50 kDa to ∼100 kDa, the protein cannot reach the inner nuclear membrane. Fluorescence recovery after photobleaching experiments of MAN1 fused to green fluorescent protein show that the fusion protein is relatively immobile in the nuclear envelope compared with the endoplasmic reticulum of interphase cells, suggesting binding to a nuclear component. These results are in agreement with the `diffusion-retention' model for targeting integral proteins to 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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