scholarly journals HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression

Blood ◽  
2014 ◽  
Vol 124 (8) ◽  
pp. 1335-1343 ◽  
Author(s):  
Xing-gang Wu ◽  
Yang Wang ◽  
Qian Wu ◽  
Wai-Hang Cheng ◽  
Wenjing Liu ◽  
...  
Keyword(s):  
Cell Surface ◽  
Proteasomal Degradation ◽  
Surface Expression ◽  
Bmp Signaling ◽  
Cell Surface Expression ◽  
Type I ◽  
Hepcidin Expression ◽  
Key Points

Key Points HFE increases Smad1/5/8 phosphorylation and hepcidin expression, and inhibition of BMP signaling abolishes HFE-induced hepcidin expression. HFE interacts with ALK3, inhibits ALK3 ubiquitination-proteasomal degradation, and increases ALK3 cell-surface expression.

scholarly journals The Level of CD81 Cell Surface Expression Is a Key Determinant for Productive Entry of Hepatitis C Virus into Host Cells

2006 ◽  
Vol 81 (2) ◽  
pp. 588-598 ◽  
Author(s):  
George Koutsoudakis ◽  
Eva Herrmann ◽  
Stephanie Kallis ◽  
Ralf Bartenschlager ◽  
Thomas Pietschmann
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Surface ◽  
Surface Expression ◽  
Hcv Infection ◽  
Host Cells ◽  
Productive Infection ◽  
Cell Surface Expression ◽  
Type I ◽  
Cell Clones

ABSTRACT Recently a cell culture model supporting the complete life cycle of the hepatitis C virus (HCV) was developed. Searching for host cell determinants involved in the HCV replication cycle, we evaluated the efficiency of virus propagation in different Huh-7-derived cell clones. We found that Huh-7.5 cells and Huh7-Lunet cells, two former replicon cell clones that had been generated by removal of an HCV replicon by inhibitor treatment, supported comparable levels of RNA replication and particle production, whereas virus spread was severely impaired in the latter cells. Analysis of cell surface expression of CD81 and scavenger receptor class B type I (SR-BI), two molecules previously implicated in HCV entry, revealed similar expression levels for SR-BI, while CD81 surface expression was much higher on Huh-7.5 cells than on Huh7-Lunet cells. Ectopic expression of CD81 in Huh7-Lunet cells conferred permissiveness for HCV infection to a level comparable to that for Huh-7.5 cells. Modulation of CD81 cell surface density in Huh-7.5 cells by RNA interference indicated that a certain amount of this molecule (∼7 × 104 molecules per cell) is required for productive infection with a low dose of HCV. Consistent with this, we show that susceptibility to HCV infection depends on a critical quantity of CD81 molecules. While infection is restricted in cells expressing very small amounts of CD81, susceptibility rapidly rises within a narrow range of CD81 levels, reaching a plateau where higher expression does not further increase the efficiency of infection. Together these data indicate that a high density of cell surface-exposed CD81 is a key determinant for productive HCV entry into host cells.

scholarly journals Analysis of the Role of N-glycosylation in Cell-surface expression, Function and Binding Properties of SARS-CoV-2 receptor ACE2

2021 ◽  
Author(s):  
Alberto Brandariz-Nuñez ◽  
Raymond R Rowland
Keyword(s):  
Cell Surface ◽  
Viral Entry ◽  
Biological Activities ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Type I ◽  
Protein Activity ◽  
Host Cell Membrane ◽  
S Protein

Human angiotensin I-converting enzyme 2 (hACE2) is a type-I transmembrane glycoprotein that serves as the major cell entry receptor for SARS-CoV and SARS-CoV-2. The viral spike (S) protein is required for attachment to ACE2 and subsequent virus-host cell membrane fusion. Previous work has demonstrated the presence of N-linked glycans in ACE2. N-glycosylation is implicated in many biological activities, including protein folding, protein activity, and cell surface expression of biomolecules. However, the contribution of N-glycosylation to ACE2 function is poorly understood. Here, we examined the role of N-glycosylation in the activity and localization of two species with different susceptibility to SARS-CoV-2 infection, porcine ACE2 (pACE2) and hACE2. The elimination of N-glycosylation by tunicamycin (TM) treatment or mutagenesis, showed that N-glycosylation is critical for the proper cell surface expression of ACE2 but not for its carboxiprotease activity. Furthermore, nonglycosylable ACE2 localized predominantly in the endoplasmic reticulum (ER) and not at the cell surface. Our data also revealed that binding of SARS-CoV and SARS-CoV-2 S protein to porcine or human ACE2 was not affected by deglycosylation of ACE2 or S proteins, suggesting that N-glycosylation plays no role in the interaction between SARS coronaviruses and the ACE2 receptor. Impairment of hACE2 N-glycosylation decreased cell to cell fusion mediated by SARS-CoV S protein but not SARS-CoV-2 S protein. Finally, we found that hACE2 N-glycosylation is required for an efficient viral entry of SARS-CoV/SARS-CoV-2 S pseudotyped viruses, which could be the result of low cell surface expression of the deglycosylated ACE2 receptor.

Metalloproteinase-mediated release of the ectodomain of L1 adhesion molecule

1999 ◽  
Vol 112 (16) ◽  
pp. 2667-2675 ◽  
Author(s):  
S. Beer ◽  
M. Oleszewski ◽  
P. Gutwein ◽  
C. Geiger ◽  
P. Altevogt
Keyword(s):  
Cell Surface ◽  
Adhesion Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Tnf Alpha ◽  
Type I ◽  
Ig Superfamily ◽  
Cell Adhesion And Migration ◽  
Membrane Bound ◽  
And Migration

The L1 adhesion molecule is an approx. 200–220 kDa type I membrane glycoprotein belonging to the immunoglobulin (Ig) superfamily. L1 can bind in a homotypic fashion and was shown to support integrin-mediated binding via RGDs in the 6th Ig-like domain. In addition to its cell-surface expression, L1 can occur in the extracellular matrix (ECM). Here we demonstrate that L1 is constitutively released from the cell surface by membrane-proximal cleavage. L1 shed from B16F10 melanoma cells remains intact and can serve as substrate for integrin-mediated cell adhesion and migration. The release of L1 occurs in mouse and human cells and is blocked by the metalloproteinase inhibitor TAPI (Immunex compound 3). This compound has been shown previously to block release of L-selectin and TNF-alpha which is mediated by the membrane-bound metalloproteinase TNF-alpha converting enzyme (TACE). Using CHO cells that are low in TACE expression and do not release L-selectin we demonstrate that L1 release is distinct from L-selectin shedding. We propose that cell-surface release may be necessary for the conversion of L1 from a membrane into an ECM protein.

Regulation of the cell-surface expression of an HTLV-I binding protein in human T cells during immune activation

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3085-3092 ◽  
Author(s):  
Manisha D. Nath ◽  
Francis W. Ruscetti ◽  
Cari Petrow-Sadowski ◽  
Kathryn S. Jones
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Cell Lines ◽  
Cd4 T Cells ◽  
Binding Protein ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Type I ◽  
Primary Cells

AbstractLittle is known about the requirements for human T-cell leukemia virus type I (HTLV-I) entry, including the identity of the cellular receptor(s). Recently, we have generated an HTLV-I surface glycoprotein (SU) immunoadhesin, HTSU-IgG, which binds specifically to cell-surface protein(s) critical for HTLV-I–mediated entry in cell lines. Here, expression of the HTLV-I SU binding protein on primary cells of the immune system was examined. The immunoadhesin specifically bound to adult T cells, B cells, NK cells, and macrophages. Cell stimulation dramatically increased the amount of binding, with the highest levels of binding on CD4+ and CD8+ T cells. Naive (CD45RAhigh, CD62Lhigh) CD4+ T cells derived from cord blood cells, in contrast to other primary cells and all cell lines examined, bound no detectable HTLV-I SU. However, following stimulation, the level of HTSU-IgG binding was rapidly induced (fewer than 6 hours), reaching the level of binding seen on adult CD4+ T cells by 72 hours. In contrast to HTLV-I virions, the soluble HTSU-IgG did not effect T-cell activation or proliferation. When incubated with human peripheral blood mononuclear cells in a mixed leukocyte reaction, HTSU-IgG inhibited proliferation at less than 1 ng/mL. These results indicate that cell-surface expression of the HTLV SU binding protein is up-regulated during in vitro activation and suggest a role for the HTLV-I SU binding proteins in the immunobiology of CD4+ T cells.

Serum Factors Inhibit Melanoma Cell Surface Expression of Type I and Type II IGF Receptors

1996 ◽  
Vol 16 (1-2) ◽  
pp. 115-134
Author(s):  
C. Bellan ◽  
M. Remacle-Bonnet ◽  
F. Garrouste ◽  
J. Secchi ◽  
J. Luis ◽  
...  
Keyword(s):  
Cell Surface ◽  
Melanoma Cell ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Type I ◽  
Type Ii ◽  
Serum Factors ◽  
Igf Receptors

Induction of B7-H6, a ligand for the natural killer cell–activating receptor NKp30, in inflammatory conditions

Blood ◽  
2013 ◽  
Vol 122 (3) ◽  
pp. 394-404 ◽  
Author(s):  
Jessica Matta ◽  
Myriam Baratin ◽  
Laurent Chiche ◽  
Jean-Marie Forel ◽  
Céline Cognet ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Cell Surface ◽  
Killer Cell ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Inflammatory Conditions ◽  
Key Points ◽  
Activating Receptor

Key Points B7-H6 transcripts, B7-H6 cell-surface expression, and sB7-H6 can be induced in inflammatory conditions in vitro and in vivo. B7-H6 is expressed on proinflammatory CD14+CD16+ monocytes in sepsis conditions and is linked to an increased mortality.

scholarly journals Cell surface expression and biosynthesis of epithelial Na+ channels

1998 ◽  
Vol 336 (3) ◽  
pp. 705-710 ◽  
Author(s):  
Lawrence S. PRINCE ◽  
Michael J. WELSH
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Hek293 Cells ◽  
Cell Surface Expression ◽  
Na Channel ◽  
Type I ◽  
Wasting Disease ◽  
Post Translational Modifications ◽  
Salt Wasting ◽  
Epithelial Na Channels

The epithelial Na+ channel (ENaC) complex is composed of three homologous subunits: α, β and γ. Mutations in ENaC subunits can increase the number of channels on the cell surface, causing a hereditary form of hypertension called Liddle's syndrome, or can decrease channel activity, causing pseudohypoaldosteronism type I, a salt-wasting disease of infancy. To investigate surface expression, we studied ENaC subunits expressed in COS-7 and HEK293 cells. Using surface biotinylation and protease sensitivity, we found that when individual ENaC subunits are expressed alone, they traffic to the cell surface. The subunits are glycosylated with high-mannose oligosaccharides, but seem to have the carbohydrate removed before they reach the cell surface. Moreover, subunits form a complex that cannot be disrupted by several non-ionic detergents. The pattern of glycosylation and detergent solubility/insolubility persists when the N-teminal and C-terminal cytoplasmic regions of ENaC are removed. With co-expression of all three ENaC subunits, the insoluble complex is the predominant species. These results show that ENaC and its family members are unique in their trafficking, biochemical characteristics and post-translational modifications.

scholarly journals Xylosyl Extension of O-Glucose Glycans on the Extracellular Domain of NOTCH1 and NOTCH2 Regulates Notch Cell Surface Trafficking

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1220 ◽  
Author(s):  
Yusuke Urata ◽  
Wataru Saiki ◽  
Yohei Tsukamoto ◽  
Hiroaki Sago ◽  
Hideharu Hibi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Consensus Sequence ◽  
Surface Expression ◽  
Notch Receptor ◽  
Cell Surface Expression ◽  
Type I ◽  
Wild Type ◽  
Double Knockout ◽  
Notch Receptors

Biochemical and genetic studies have indicated that O-linked glycosylation such as O-glucose (Glc), fucose (Fuc), and N-acetylglucosamine (GlcNAc) is critical for Notch signaling; however, it is not fully understood how O-glycans regulate the Notch receptor function. Notch receptors are type-I transmembrane proteins with large extracellular domains (ECD), containing 29–36 epidermal growth factor-like (EGF) repeats. Here, we analyzed O-Glc glycans on NOTCH1 and NOTCH2 expressed in HEK293T cells using an Orbitrap Fusion mass spectrometer and successfully revealed the structures and stoichiometries of all 17 EGF repeats of NOTCH1 with the O-Glc consensus sequence (C1-X-S-X-(P/A)-C2), and 16 out of 17 EGF repeats of NOTCH2 with the same consensus sequence. High levels of O-Glc attachment and xylosyl elongation were detected on most NOTCH1 and NOTCH2 EGF repeats. When both glucoside xylosyltransferases, GXYLT1 and GXYLT2, responsible for the xylosyl elongation of O-glucose, were genetically deleted, the expression of endogenous NOTCH1 and NOTCH2 on the surface of HEK293T cells did not change, but the cell surface expression of overexpressed NOTCH1 and NOTCH2 decreased compared with that in the wild type cells. In vitro secretion assays consistently showed a reduced secretion of both the NOTCH1 and NOTCH2 ECDs in GXYLT1 and GXYLT2 double knockout cells compared with the wild type cells, suggesting a significant role of the elongation of O-Glc glycans on the Notch ECDs in the quality control of Notch receptors.

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