Cyto-friendly polymerization at cell surfaces modulates cell fate by clustering cell-surface receptors

Cell-surface polymerization of anti-CD20 aptamer modified macromer to induce CD20 receptor clustering, and effectively initiate the apoptotic signals in cells.

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FGF1 Fusions with the Fc Fragment of IgG1 for the Assembly of GFPpolygons-Mediated Multivalent Complexes Recognizing FGFRs

Biomolecules ◽

10.3390/biom11081088 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1088

Author(s):

Marta Poźniak ◽

Weronika Zarzycka ◽

Natalia Porębska ◽

Agata Knapik ◽

Paulina Marczakiewicz-Perera ◽

...

Keyword(s):

Cell Surface ◽

Cell Fate ◽

Biologically Active ◽

Fine Tuning ◽

Cell Surface Receptors ◽

Fc Fragment ◽

Surface Receptors ◽

Cellular Processes ◽

Novel Approach ◽

Trigger Receptor

FGFRs are cell surface receptors that, when activated by specific FGFs ligands, transmit signals through the plasma membrane, regulating key cellular processes such as differentiation, division, motility, metabolism and death. We have recently shown that the modulation of the spatial distribution of FGFR1 at the cell surface constitutes an additional mechanism for fine-tuning cellular signaling. Depending on the multivalent, engineered ligand used, the clustering of FGFR1 into diverse supramolecular complexes enhances the efficiency and modifies the mechanism of receptor endocytosis, alters FGFR1 lifetime and modifies receptor signaling, ultimately determining cell fate. Here, we present a novel approach to generate multivalent FGFR1 ligands. We functionalized FGF1 for controlled oligomerization by developing N- and C-terminal fusions of FGF1 with the Fc fragment of human IgG1 (FGF1-Fc and Fc-FGF1). As oligomerization scaffolds, we employed GFPpolygons, engineered GFP variants capable of well-ordered multivalent display, fused to protein G to ensure binding of Fc fragment. The presented strategy allows efficient assembly of oligomeric FGFR1 ligands with up to twelve receptor binding sites. We show that multivalent FGFR1 ligands are biologically active and trigger receptor clustering on the cell surface. Importantly, the approach described in this study can be easily adapted to oligomerize alternative growth factors to control the activity of other cell surface receptors.

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Receptor clustering and activation by multivalent interaction through recognition peptides presented on exosomes

Chemical Communications ◽

10.1039/c6cc06719k ◽

2017 ◽

Vol 53 (2) ◽

pp. 317-320 ◽

Cited By ~ 14

Author(s):

I. Nakase ◽

N. Ueno ◽

M. Katayama ◽

K. Noguchi ◽

T. Takatani-Nakase ◽

...

Keyword(s):

Cell Surface ◽

Receptor Activation ◽

Cell Surface Receptors ◽

Receptor Clustering ◽

Surface Receptors ◽

Peptide Segments

A system for inducing clustering of cell surface receptors via recognition peptide segments displayed on exosomes, leading to receptor activation.

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Receptor Tyrosine Kinases in Development: Insights from Drosophila

International Journal of Molecular Sciences ◽

10.3390/ijms21010188 ◽

2019 ◽

Vol 21 (1) ◽

pp. 188 ◽

Cited By ~ 1

Author(s):

Sarah Mele ◽

Travis K. Johnson

Keyword(s):

Cell Surface ◽

Cell Fate ◽

Tyrosine Kinases ◽

Cell Biology ◽

Receptor Tyrosine Kinases ◽

Cell Communication ◽

Model Organisms ◽

Cell Surface Receptors ◽

Surface Receptors ◽

Cell Fate Decisions

Cell-to-cell communication mediates a plethora of cellular decisions and behaviors that are crucial for the correct and robust development of multicellular organisms. Many of these signals are encoded in secreted hormones or growth factors that bind to and activate cell surface receptors, to transmit the cue intracellularly. One of the major superfamilies of cell surface receptors are the receptor tyrosine kinases (RTKs). For nearly half a century RTKs have been the focus of intensive study due to their ability to alter fundamental aspects of cell biology, such as cell proliferation, growth, and shape, and because of their central importance in diseases such as cancer. Studies in model organisms such a Drosophila melanogaster have proved invaluable for identifying new conserved RTK pathway components, delineating their contributions, and for the discovery of conserved mechanisms that control RTK-signaling events. Here we provide a brief overview of the RTK superfamily and the general mechanisms used in their regulation. We further highlight the functions of several RTKs that govern distinct cell-fate decisions in Drosophila and explore how their activities are developmentally controlled.

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Constitutive Activating and Inactivating Mutants of Eel Luteinizing Hormone Receptor

10.20944/preprints202009.0185.v1 ◽

2020 ◽

Author(s):

Munkhzaya Byambaragchaa ◽

Dong-An Kim ◽

Dae-Jung Kim ◽

Sun-Mee Hong ◽

Myung-Hwa Kang ◽

...

Keyword(s):

Signal Transduction ◽

Luteinizing Hormone ◽

Cell Surface ◽

Hormone Receptor ◽

Luteinizing Hormone Receptor ◽

Cell Surface Receptors ◽

Wild Type ◽

Surface Receptors ◽

Agonist Stimulation ◽

In Cells

We analyzed signal transduction of three constitutively activating mutants (M410T, L469R, and D590Y) and two inactivating mutants (D417N and Y558F) of the eel luteinizing hormone receptor (eel LHR), known to occur in human LHR. The objective of this study was to assess the functional effects of these mutations in signal transduction and cell surface loss of receptor. Mutant receptors were transiently expressed in Chinese hamster ovary (CHO-K1) cells. Eel LH-stimulated accumulation of cyclic adenosine monophosphate (cAMP) was measured by homogeneous time-resolved fluorescence (HTRF) assays. The loss of receptors from the cells surface was measured using an enzyme-linked immunosorbent assay (ELISA) in human embryonic kidney (HEK) 293 cells. The cAMP response in cells expressing the wild type eel LHR was increased in a dose-dependent manner using eel LH ligand stimulation. Compared with the wild type, cells expressing the activating mutants (M410T, L469R, and D590Y), exhibited a 4.0-, 19.1-, and 7.8-fold increase in basal cAMP response without agonist stimulation, respectively. Their maximal responses to agonist stimulation were approximately 65%, 52%, and 98%, respectively, of those of the wild type. The inactivating mutants (D417N and Y558F) did not completely impair signal transduction, and their maximal responses were only 33% and25 % of those of wild type. These data clearly showed that the eel LHR-L469R and D590Y, activating mutants enhanced the rate of the loss of cell surface receptors following treatment with eel LH. Thus, the loss of cell surface receptors in cells expressing mutant eel LHRs was consistent with the eel LH agonist-induced production of cAMP. Our results suggested that the activation of the eel LHR requires appropriate loss of LHR-ligand complexes from the cell surface.

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