scholarly journals Transmembrane protein TMEM170A is a newly discovered regulator of ER and nuclear envelope morphogenesis in human cells

2016 ◽  
Vol 129 (8) ◽  
pp. 1552-1565 ◽  
Author(s):  
Andri Christodoulou ◽  
Rachel Santarella-Mellwig ◽  
Niovi Santama ◽  
Iain W. Mattaj
Keyword(s):  
Nuclear Envelope ◽  
Transmembrane Protein ◽  
Human Cells

3D3/lyric: a novel transmembrane protein of the endoplasmic reticulum and nuclear envelope, which is also present in the nucleolus

2004 ◽  
Vol 294 (1) ◽  
pp. 94-105 ◽  
Author(s):  
Heidi G.E Sutherland ◽  
Yun Wah Lam ◽  
Stephanie Briers ◽  
Angus I Lamond ◽  
Wendy A Bickmore
Keyword(s):  
Endoplasmic Reticulum ◽  
Nuclear Envelope ◽  
Transmembrane Protein

scholarly journals LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells

2017 ◽  
Vol 114 (11) ◽  
pp. E2166-E2175 ◽  
Author(s):  
Mingyu Gu ◽  
Dollie LaJoie ◽  
Opal S. Chen ◽  
Alexander von Appen ◽  
Mark S. Ladinsky ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Fission Yeast ◽  
Nuclear Membrane ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Human Cells ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Loss Of Function

Endosomal sorting complexes required for transport III (ESCRT-III) proteins have been implicated in sealing the nuclear envelope in mammals, spindle pole body dynamics in fission yeast, and surveillance of defective nuclear pore complexes in budding yeast. Here, we report that Lem2p (LEM2), a member of the LEM (Lap2-Emerin-Man1) family of inner nuclear membrane proteins, and the ESCRT-II/ESCRT-III hybrid protein Cmp7p (CHMP7), work together to recruit additional ESCRT-III proteins to holes in the nuclear membrane. InSchizosaccharomyces pombe, deletion of the ATPasevps4leads to severe defects in nuclear morphology and integrity. These phenotypes are suppressed by loss-of-function mutations that arise spontaneously inlem2orcmp7, implying that these proteins may function upstream in the same pathway. Building on these genetic interactions, we explored the role of LEM2 during nuclear envelope reformation in human cells. We found that CHMP7 and LEM2 enrich at the same region of the chromatin disk periphery during this window of cell division and that CHMP7 can bind directly to the C-terminal domain of LEM2 in vitro. We further found that, during nuclear envelope formation, recruitment of the ESCRT factors CHMP7, CHMP2A, and IST1/CHMP8 all depend on LEM2 in human cells. We conclude that Lem2p/LEM2 is a conserved nuclear site-specific adaptor that recruits Cmp7p/CHMP7 and downstream ESCRT factors to the nuclear envelope.

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 Yeast as a Tool for Deeper Understanding of Human Manganese-Related Diseases

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 545
Author(s):  
Thines ◽  
Deschamps ◽  
Stribny ◽  
Morsomme
Keyword(s):  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Friedreich Ataxia ◽  
Human Cells ◽  
Congenital Disorder ◽  
Yeast Cells ◽  
Enzymatic Antioxidant ◽  
Congenital Disorder Of Glycosylation ◽  
Biological Importance ◽  
Insight Into

The biological importance of manganese lies in its function as a key cofactor for numerous metalloenzymes and as non-enzymatic antioxidant. Due to these two essential roles, it appears evident that disturbed manganese homeostasis may trigger the development of pathologies in humans. In this context, yeast has been extensively used over the last decades to gain insight into how cells regulate intra-organellar manganese concentrations and how human pathologies may be related to disturbed cellular manganese homeostasis. This review first summarizes how manganese homeostasis is controlled in yeast cells and how this knowledge can be extrapolated to human cells. Several manganese-related pathologies whose molecular mechanisms have been studied in yeast are then presented in the light of the function of this cation as a non-enzymatic antioxidant or as a key cofactor of metalloenzymes. In this line, we first describe the Transmembrane protein 165-Congenital Disorder of Glycosylation (TMEM165-CDG) and Friedreich ataxia pathologies. Then, due to the established connection between manganese cations and neurodegeneration, the Kufor–Rakeb syndrome and prion-related diseases are finally presented.

scholarly journals Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane

2008 ◽  
Vol 180 (4) ◽  
pp. 763-769 ◽  
Author(s):  
Miki Hieda ◽  
Mayumi Isokane ◽  
Michiko Koizumi ◽  
Chiduru Higashi ◽  
Taro Tachibana ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Transmembrane Protein ◽  
Active Form ◽  
Type I ◽  
Transcriptional Repressors ◽  
Sequence Element ◽  
Inner Nuclear Membrane

Heparin-binding EGF-like growth factor (HB-EGF) is synthesized as a type I transmembrane protein (proHB-EGF) and expressed on the cell surface. The ectodomain shedding of proHB-EGF at the extracellular region on the plasma membrane yields a soluble EGF receptor ligand and a transmembrane-cytoplasmic fragment (HB-EGF-CTF). The cytoplasmic domain of proHB-EGF (HB-EGF-cyto) interacts with transcriptional repressors to reverse their repressive activities. However, how HB-EGF-cyto accesses transcriptional repressors is yet unknown. The present study demonstrates that, after exposure to shedding stimuli, both HB-EGF-CTF and unshed proHB-EGF translocate to the nuclear envelope. Immunoelectron microscopy and digitonin-permeabilized cells showed that HB-EGF-cyto signals are at the inner nuclear membrane. A short sequence element within the HB-EGF-cyto allows a transmembrane protein to localize to the nuclear envelope. The dominant-active form of Rab5 and Rab11 suppressed nuclear envelope targeting. Collectively, these data demonstrate that membrane-anchored HB-EGF is targeted to the inner nuclear membrane via a retrograde membrane trafficking pathway.

scholarly journals High-Throughput Identification of Nuclear Envelope Protein Interactions in Schizosaccharomyces pombe Using an Arrayed Membrane Yeast-Two Hybrid Library

2020 ◽  
Vol 10 (12) ◽  
pp. 4649-4663 ◽  
Author(s):  
Joseph M. Varberg ◽  
Jennifer M. Gardner ◽  
Scott McCroskey ◽  
Snehabala Saravanan ◽  
William D. Bradford ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Nuclear Envelope ◽  
Schizosaccharomyces Pombe ◽  
High Throughput ◽  
Protein Interactions ◽  
Transmembrane Protein ◽  
Integral Membrane Proteins ◽  
Model Organisms ◽  
Yeast Two Hybrid ◽  
Two Hybrid

The nuclear envelope (NE) contains a specialized set of integral membrane proteins that maintain nuclear shape and integrity and influence chromatin organization and gene expression. Advances in proteomics techniques and studies in model organisms have identified hundreds of proteins that localize to the NE. However, the function of many of these proteins at the NE remains unclear, in part due to a lack of understanding of the interactions that these proteins participate in at the NE membrane. To assist in the characterization of NE transmembrane protein interactions we developed an arrayed library of integral and peripheral membrane proteins from the fission yeast Schizosaccharomyces pombe for high-throughput screening using the split-ubiquitin based membrane yeast two -hybrid system. We used this approach to characterize protein interactions for three conserved proteins that localize to the inner nuclear membrane: Cut11/Ndc1, Lem2 and Ima1/Samp1/Net5. Additionally, we determined how the interaction network for Cut11 is altered in canonical temperature-sensitive cut11-ts mutants. This library and screening approach is readily applicable to characterizing the interactomes of integral membrane proteins localizing to various subcellular compartments.

scholarly journals Distribution and induction of cytochrome P-450 in rat liver nuclear envelope.

1981 ◽  
Vol 91 (1) ◽  
pp. 212-220 ◽  
Author(s):  
S Matsuura ◽  
R Masuda ◽  
K Omori ◽  
M Negishi ◽  
Y Tashiro
Keyword(s):  
Nuclear Envelope ◽  
Outer Membrane ◽  
Rat Liver ◽  
Molecular Species ◽  
Transmembrane Protein ◽  
Microscopic Analysis ◽  
Inner Membrane ◽  
Cytoplasmic Face ◽  
Biochemical Analyses ◽  
Cytochrome P 450

Induction of cytochrome P-450s by 3-methylcholanthrene (MC) and phenobarbital (PB) and distribution of P-450s in the rat liver nuclear envelope were investigated by biochemical analyses and ferritin immunoelectron microscopy using specific antibodies against the major molecular species of MC- and PB-induced cytochrome P-450. It was found, in agreement with Kasper (J. Biol. Chem., 1971, 246: 577-581), that the total amount of cytochrome P-450s determined by biochemical analysis was markedly increased by MC, but not by PB, treatment. Immunoelectron microscopic analysis, however, showed marked and slight increases in ferritin labeling by MC and PB treatment, respectively. The latter finding was interpreted as resulting from the induction of a particular molecular species of PB-induced cytochrome P-450s. Ferritin immunoelectron microscopic analysis of intact isolated nuclei, naked nuclei from which the outer membrane of the nuclear envelope was partially detached (mechanically), and isolated nuclear envelopes have shown that the ferritin particles are found exclusively on the cytoplasmic face of the outer nuclear envelopes. Neither the nucleoplasmic face of the inner membrane of the nuclear envelope nor the cisternal face of both membranes of the nuclear envelope showed any labeling with ferritin. This indicates that cytochrome P-450 is located only on the outer membrane of the nuclear envelope and does not diffuse laterally into the domain of the inner membrane of the nuclear envelope across the nuclear pores. Our results suggest that a marked heterogeneity exists in the enzyme distribution between the outer and inner membrane of the nuclear envelope and that microsomal marker enzymes such as cytochrome P-450 exist exclusively in the outer membrane. In addition, it appears that cytochrome P-450 is probably not a transmembrane protein but an intrinsic protein located on the cytoplasmic face of the outer membrane of the nuclear envelope.

unc-83encodes a novel component of the nuclear envelope and is essential for proper nuclear migration

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 5039-5050 ◽  
Author(s):  
Daniel A. Starr ◽  
Greg J. Hermann ◽  
Christian J. Malone ◽  
William Fixsen ◽  
James R. Priess ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Essential Role ◽  
Transmembrane Protein ◽  
Nuclear Lamina ◽  
Nuclear Migration ◽  
C Elegans ◽  
Specific Manner ◽  
Sun Domain ◽  
P Cells

Nuclear migration plays an essential role in the growth and development of a wide variety of eukaryotes. Mutations in unc-84, which encodes a conserved component of the nuclear envelope, have been shown to disrupt nuclear migration in two C. elegans tissues. We show that mutations in unc-83 disrupt nuclear migration in a similar manner in migrating P cells, hyp7 precursors and the intestinal primordium, but have no obvious defects in the association of centrosomes with nuclei or the structure of the nuclear lamina of migrating nuclei. We also show that unc-83 encodes a novel transmembrane protein. We identified three unc-83 transcripts that are expressed in a tissue-specific manner. Antibodies against UNC-83 co-localized to the nuclear envelope with lamin and UNC-84. Unlike UNC-84, UNC-83 localized to only specific nuclei, many of which were migratory. UNC-83 failed to localize to the nuclear envelope in unc-84 mutants with lesions in the conserved SUN domain of UNC-84, and UNC-83 interacted with the SUN domain of UNC-84 in vitro, suggesting that these two proteins function together during nuclear migration. We favor a model in which UNC-84 directly recruits UNC-83 to the nuclear envelope where they help transfer force between the cytoskeleton and the nucleus.

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