scholarly journals Cell surface annexins regulate ADAM-mediated ectodomain shedding of proamphiregulin

2012 ◽  
Vol 23 (10) ◽  
pp. 1964-1975 ◽  
Author(s):  
Hironao Nakayama ◽  
Shinji Fukuda ◽  
Hirofumi Inoue ◽  
Hisayo Nishida-Fukuda ◽  
Yuji Shirakata ◽  
...  
Keyword(s):  
Cell Surface ◽  
Therapeutic Potential ◽  
Growth Factor Receptor ◽  
Ultraviolet B ◽  
Ectodomain Shedding ◽  
Substrate Selectivity ◽  
Primary Keratinocytes ◽  
Egfr Ligands ◽  
Epidermal Growth ◽  
A Disintegrin And Metalloproteinase

A disintegrin and metalloproteinase (ADAM) is a family of enzymes involved in ectodomain shedding of various membrane proteins. However, the molecular mechanism underlying substrate recognition by ADAMs remains unknown. In this study, we successfully captured and analyzed cell surface transient assemblies between the transmembrane amphiregulin precursor (proAREG) and ADAM17 during an early shedding phase, which enabled the identification of cell surface annexins as components of their shedding complex. Annexin family members annexin A2 (ANXA2), A8, and A9 interacted with proAREG and ADAM17 on the cell surface. Shedding of proAREG was increased when ANXA2 was knocked down but decreased with ANXA8 and A9 knockdown, because of enhanced and impaired association with ADAM17, respectively. Knockdown of ANXA2 and A8 in primary keratinocytes altered wound-induced cell migration and ultraviolet B–induced phosphorylation of epidermal growth factor receptor (EGFR), suggesting that annexins play an essential role in the ADAM-mediated ectodomain shedding of EGFR ligands. On the basis of these data, we propose that annexins on the cell surface function as “shedding platform” proteins to determine the substrate selectivity of ADAM17, with possible therapeutic potential in ADAM-related diseases.

scholarly journals Vaccinia Virus Interactions with the Cell Membrane Studied by New Chromatic Vesicle and Cell Sensor Assays

2006 ◽  
Vol 81 (3) ◽  
pp. 1140-1147 ◽  
Author(s):  
Z. Orynbayeva ◽  
S. Kolusheva ◽  
N. Groysman ◽  
N. Gavrielov ◽  
L. Lobel ◽  
...  
Keyword(s):  
Cell Surface ◽  
Vaccinia Virus ◽  
Lipid Bilayers ◽  
Growth Factor Receptor ◽  
Viral Envelope ◽  
Virus Infectivity ◽  
Membrane Interactions ◽  
Viral Interactions ◽  
Epidermal Growth ◽  
Virus Interactions

ABSTRACT The potential danger of cross-species viral infection points to the significance of understanding the contributions of nonspecific membrane interactions with the viral envelope compared to receptor-mediated uptake as a factor in virus internalization and infection. We present a detailed investigation of the interactions of vaccinia virus particles with lipid bilayers and with epithelial cell membranes using newly developed chromatic biomimetic membrane assays. This analytical platform comprises vesicular particles containing lipids interspersed within reporter polymer units that emit intense fluorescence following viral interactions with the lipid domains. The chromatic vesicles were employed as membrane models in cell-free solutions and were also incorporated into the membranes of epithelial cells, thereby functioning as localized membrane sensors on the cell surface. These experiments provide important insight into membrane interactions with and fusion of virions and the kinetic profiles of these processes. In particular, the data emphasize the significance of cholesterol/sphingomyelin domains (lipid rafts) as a crucial factor promoting bilayer insertion of the viral particles. Our analysis of virus interactions with polymer-labeled living cells exposed the significant role of the epidermal growth factor receptor in vaccinia virus infectivity; however, the data also demonstrated the existence of additional non-receptor-mediated mechanisms contributing to attachment of the virus to the cell surface and its internalization.

scholarly journals Cell surface fibroblast growth factor and epidermal growth factor receptors are permanently lost during skeletal muscle terminal differentiation in culture.

1988 ◽  
Vol 107 (2) ◽  
pp. 761-769 ◽  
Author(s):  
B B Olwin ◽  
S D Hauschka
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Growth Factor Receptors ◽  
Skeletal Muscle Differentiation ◽  
Fibroblast Growth ◽  
Epidermal Growth

One characteristic of skeletal muscle differentiation is the conversion of proliferating cells to a population that is irreversibly postmitotic. This developmental change can be induced in vitro by depriving the cultures of specific mitogens such as fibroblast growth factor (FGF). Analysis of cell surface FGF receptor (FGFR) in several adult mouse muscle cell lines and epidermal growth factor receptor (EGFR) in mouse MM14 cells reveals a correlation between receptor loss and the acquisition of a postmitotic phenotype. Quiescent MM14 cells, mitogen-depleted, differentiation-defective MM14 cells, and differentiated BC3H1 muscle cells (a line that fails to become postmitotic upon differentiation) retained their cell surface FGFR. These results indicate that FGFR loss is not associated with either reversible cessation of muscle cell proliferation or biochemical differentiation and thus, further support a correlation between receptor loss and acquisition of a postmitotic phenotype. Comparison of the kinetics for growth factor receptor loss and for commitment of MM14 cells to a postmitotic phenotype reveals that FGFR rises transiently from approximately 700 receptors/cell to a maximum of approximately 2,000 receptors/cell 12 h after FGF removal, when at the same time, greater than 95% of the cells are postmitotic. FGFR levels then decline to undetectable levels by 24 h after FGF removal. During the interval in which FGFR increases and then disappears there is no change in its affinity for FGF. The transient increase in growth factor receptors appears to be due to a decrease in ligand-mediated internalization because EGFR, which undergoes an immediate decline when cultures are deprived of FGF (Lim, R. W., and S. D. Hauschka. 1984. J. Cell Biol. 98:739-747), exhibits a similar transient rise when cultures are grown in media containing both EGF and FGF before switching the cells to media without these added factors. These results indicate that the loss of certain growth factor receptors is a specific phenotype acquired during skeletal muscle differentiation, but they do not resolve whether regulation of FGFR number is causal for initiation of the postmitotic phenotype. A general model is presented in the discussion.

scholarly journals Enterophilin-1, a New Partner of Sorting Nexin 1, Decreases Cell Surface Epidermal Growth Factor Receptor

2003 ◽  
Vol 278 (23) ◽  
pp. 21155-21161 ◽  
Author(s):  
Véronique Pons ◽  
Françoise Hullin-Matsuda ◽  
Michel Nauze ◽  
Ronald Barbaras ◽  
Christine Pérès ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptor ◽  
Sorting Nexin ◽  
Epidermal Growth ◽  
Sorting Nexin 1

scholarly journals ADAM17 stabilizes its interacting partner inactive Rhomboid 2 (iRhom2) but not inactive Rhomboid 1 (iRhom1)

2020 ◽  
Vol 295 (13) ◽  
pp. 4350-4358 ◽  
Author(s):  
Gisela Weskamp ◽  
Johanna Tüshaus ◽  
Daniel Li ◽  
Regina Feederle ◽  
Thorsten Maretzky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Surface ◽  
Growth Factor Receptor ◽  
Interleukin 6 Receptor ◽  
Epidermal Growth ◽  
Primary Bone ◽  
Endogenous Proteins ◽  
Membrane Spanning ◽  
Factor Α ◽  
And Function

The metalloprotease ADAM17 (a disintegrin and metalloprotease 17) is a key regulator of tumor necrosis factor α (TNFα), interleukin 6 receptor (IL-6R), and epidermal growth factor receptor (EGFR) signaling. ADAM17 maturation and function depend on the seven-membrane–spanning inactive rhomboid-like proteins 1 and 2 (iRhom1/2 or Rhbdf1/2). Most studies to date have focused on overexpressed iRhom1 and -2, so only little is known about the properties of the endogenous proteins. Here, we show that endogenous iRhom1 and -2 can be cell surface–biotinylated on mouse embryonic fibroblasts (mEFs), revealing that endogenous iRhom1 and -2 proteins are present on the cell surface and that iRhom2 also is present on the surface of lipopolysaccharide-stimulated primary bone marrow–derived macrophages. Interestingly, very little, if any, iRhom2 was detectable in mEFs or bone marrow–derived macrophages lacking ADAM17, suggesting that iRhom2 is stabilized by ADAM17. By contrast, the levels of iRhom1 were slightly increased in the absence of ADAM17 in mEFs, indicating that its stability does not depend on ADAM17. These findings support a model in which iRhom2 and ADAM17 are obligate binding partners and indicate that iRhom2 stability requires the presence of ADAM17, whereas iRhom1 is stable in the absence of ADAM17.

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