scholarly journals Programming cell surface signaling via phase separation-controlled compartmentalization

2021 ◽  
Author(s):  
Ru Li ◽  
Tiantian Li ◽  
Genzhe Lu ◽  
Zhi Cao ◽  
Bowen Chen ◽  
...  
Keyword(s):  
Phase Separation ◽  
Cell Surface ◽  
Surface Proteins ◽  
Membrane Recruitment ◽  
Separation Systems ◽  
Membrane Tethering ◽  
Surface Signaling ◽  
Cell Surface Signaling ◽  
Orthogonal Phase ◽  
Liquid Liquid Phase Separation

Abstract Cell surface signaling landscapes are formidably complex. Robust tools capable of manipulating the spatiotemporal distribution of cell surface proteins (CSPs) for dissecting signaling are in high demand. Some CSPs are regulated via multivalency-driven liquid-liquid phase separation (LLPS). Employing the robustness and versatility of LLPS, we decided to engineer LLPS-based tools for precisely manipulating CSPs. We generated membrane-tethering LLPS systems by fusing multivalent modular phase separation scaffold pairs with CSP binders. Phase separation of the scaffold pairs, concomitant compartmentalization of CSPs on membranes, and cluster-dependent signaling outputs of CSPs require membrane recruitment of one or both scaffolds. We also engineered orthogonal phase separation systems to segregate CSPs into mutually exclusive compartments. The engineered phase separation systems can robustly cluster individual CSPs, co-cluster two or more CSPs, or segregate different CSPs into distinct compartments on cell surfaces. These novel tools will enable the dissection of complicated cell signaling landscapes with unprecedented precision.

scholarly journals Human tumor-derived exosomes (TEX) regulate Treg functions via cell surface signaling rather than uptake mechanisms

2017 ◽  
Vol 6 (8) ◽  
pp. e1261243 ◽  
Author(s):  
Laurent Muller ◽  
Patricia Simms ◽  
Chang-Sook Hong ◽  
Michael I. Nishimura ◽  
Edwin K. Jackson ◽  
...  
Keyword(s):  
Cell Surface ◽  
Human Tumor ◽  
Surface Signaling ◽  
Cell Surface Signaling ◽  
Uptake Mechanisms

Observing Cell Surface Signaling Domains Using Electron Microscopy

2003 ◽  
Vol 2003 (177) ◽  
pp. pl9-pl9 ◽  
Author(s):  
I. A. Prior ◽  
R. G. Parton ◽  
J. F. Hancock
Keyword(s):  
Electron Microscopy ◽  
Cell Surface ◽  
Surface Signaling ◽  
Cell Surface Signaling ◽  
Signaling Domains

scholarly journals Role of Cell Surface Signaling in Proteolysis of an Alternative Sigma Factor in Pseudomonas aeruginosa

2008 ◽  
Vol 190 (14) ◽  
pp. 4865-4869 ◽  
Author(s):  
Matthew R. Spencer ◽  
Paul A. Beare ◽  
Iain L. Lamont
Keyword(s):  
Cell Surface ◽  
Signaling Pathway ◽  
Sigma Factor ◽  
Receptor Protein ◽  
Proteolytic Degradation ◽  
Alternative Sigma Factor ◽  
A Cell ◽  
Surface Signaling ◽  
Cell Surface Signaling ◽  
Antisigma Factor

ABSTRACT Alternative sigma factor proteins enable transcription of specific sets of genes in bacterial cells. Their activities can be controlled by posttranslational mechanisms including inhibition by antisigma proteins and proteolytic degradation. PvdS is an alternative sigma factor that is required for expression of genes involved in synthesis of a siderophore, pyoverdine, by Pseudomonas aeruginosa. In the absence of pyoverdine, the activity of PvdS is inhibited by a membrane-spanning antisigma factor, FpvR. Inhibition is relieved by a cell surface signaling pathway. In this pathway, a combination of pyoverdine and a cell surface receptor protein, FpvA, suppresses the antisigma activity of FpvR, enabling transcription of PvdS-dependent genes. In this research, we investigated proteolytic degradation of PvdS in response to the signaling pathway. Proteolysis of PvdS was observed in strains of P. aeruginosa in which FpvR had anti-sigma factor activity due to the absence of pyoverdine or the FpvA receptor protein or overproduction of FpvR. Suppression of antisigma activity by addition of pyoverdine or through the absence of FpvR prevented detectable proteolysis of PvdS. The amounts of PvdS were less in bacteria in which proteolysis was observed, and reporter gene assays showed that this reduction was not due to decreased expression of PvdS. In wild-type bacteria, there was an average of 730 molecules of PvdS per cell in late exponential growth phase. Our results show that proteolysis and amounts of PvdS are affected by the antisigma factor FpvR and that this activity of FpvR is controlled by the cell surface signaling pathway.

scholarly journals N-Acetylglucosamine Functions in Cell Signaling

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
James B. Konopka
Keyword(s):  
Cell Wall ◽  
Cell Surface ◽  
Cell Signaling ◽  
Amino Sugar ◽  
Animal Cells ◽  
Fungal Cell ◽  
E Coli ◽  
Human Fungal Pathogen ◽  
Surface Signaling ◽  
Cell Surface Signaling

The amino sugar N-acetylglucosamine (GlcNAc) is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogenCandida albicansto undergo changes in morphogenesis and expression of virulence genes. PathogenicE. coliresponds to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the posttranslational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc, and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this paper.

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