CellTalkDB: a manually curated database of ligand–receptor interactions in humans and mice

2020 ◽  
Author(s):  
Xin Shao ◽  
Jie Liao ◽  
Chengyu Li ◽  
Xiaoyan Lu ◽  
Junyun Cheng ◽  
...  
Keyword(s):  
Single Cell ◽  
Protein Interactions ◽  
Cell Communication ◽  
Systematic Investigation ◽  
Protein Protein Interactions ◽  
Biological Phenomena ◽  
Type Composition ◽  
Dependent Cell ◽  
Multicellular Organisms ◽  
Cell Cell

Abstract Cell–cell communications in multicellular organisms generally involve secreted ligand–receptor (LR) interactions, which is vital for various biological phenomena. Recent advancements in single-cell RNA sequencing (scRNA-seq) have effectively resolved cellular phenotypic heterogeneity and the cell-type composition of complex tissues, facilitating the systematic investigation of cell–cell communications at single-cell resolution. However, assessment of chemical-signal-dependent cell–cell communication through scRNA-seq relies heavily on prior knowledge of LR interaction pairs. We constructed CellTalkDB (http://tcm.zju.edu.cn/celltalkdb), a manually curated comprehensive database of LR interaction pairs in humans and mice comprising 3398 human LR pairs and 2033 mouse LR pairs, through text mining and manual verification of known protein–protein interactions using the STRING database, with literature-supported evidence for each pair. Compared with SingleCellSignalR, the largest LR-pair resource, CellTalkDB includes not only 2033 mouse LR pairs but also 377 additional human LR pairs. In conclusion, the data on human and mouse LR pairs contained in CellTalkDB could help to further the inference and understanding of the LR-interaction-based cell–cell communications, which might provide new insights into the mechanism underlying biological processes.

scholarly journals New avenues for systematically inferring cell-cell communication: through single-cell transcriptomics data

2020 ◽  
Vol 11 (12) ◽  
pp. 866-880 ◽  
Author(s):  
Xin Shao ◽  
Xiaoyan Lu ◽  
Jie Liao ◽  
Huajun Chen ◽  
Xiaohui Fan
Keyword(s):  
Single Cell ◽  
Communication Networks ◽  
Cell Communication ◽  
Receptor Interaction ◽  
Communication Studies ◽  
Transcriptomics Data ◽  
Phenotype Heterogeneity ◽  
Multicellular Organisms ◽  
Communication Study ◽  
Cell Cell

AbstractFor multicellular organisms, cell-cell communication is essential to numerous biological processes. Drawing upon the latest development of single-cell RNA-sequencing (scRNA-seq), high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues, which enables systematic cell-cell communication studies at a single-cell level. We first summarize a common workflow of cell-cell communication study using scRNA-seq data, which often includes data preparation, construction of communication networks, and result validation. Two common strategies taken to uncover cell-cell communications are reviewed, e.g., physically vicinal structure-based and ligand-receptor interaction-based one. To conclude, challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.

Characterization of the interactions of alpha-catenin with alpha-actinin and beta-catenin/plakoglobin

1997 ◽  
Vol 110 (8) ◽  
pp. 1013-1022 ◽  
Author(s):  
J.E. Nieset ◽  
A.R. Redfield ◽  
F. Jin ◽  
K.A. Knudsen ◽  
K.R. Johnson ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Protein Interactions ◽  
Beta Catenin ◽  
Protein Protein Interactions ◽  
Yeast Two Hybrid ◽  
Calcium Dependent ◽  
Cytoplasmic Proteins ◽  
Dependent Cell ◽  
Two Hybrid ◽  
Cell Cell

Cadherins are calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. To function in cell-cell adhesion, the transmembrane cadherin molecule must be associated with the cytoskeleton via cytoplasmic proteins known as catenins. Three catenins, alpha-catenin, beta-catenin and gamma-catenin (also known as plakoglobin), have been identified. beta-catenin or plakoglobin is associated directly with the cadherin; alpha-catenin binds to beta-catenin/plakoglobin and serves to link the cadherin/catenin complex to the actin cytoskeleton. The domains on the cadherin and betacatenin/plakoglobin that are responsible for protein-protein interactions have been mapped. However, little is known about the molecular interactions between alpha-catenin and beta-catenin/plakoglobin or about the interactions between alpha-catenin and the cytoskeleton. In this study we have used the yeast two-hybrid system to map the domains on alpha-catenin that allow it to associate with beta-catenin/plakoglobin and with alpha-actinin. We also identify a region on alpha-actinin that is responsible for its interaction with alpha-catenin. The yeast two-hybrid data were confirmed with biochemical studies.

scholarly journals Cellinker: a platform of ligand–receptor interactions for intercellular communication analysis

2021 ◽  
Author(s):  
Yang Zhang ◽  
Tianyuan Liu ◽  
Jing Wang ◽  
Bohao Zou ◽  
Le Li ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Intercellular Communication ◽  
Rapid Development ◽  
Cell Communication ◽  
Supplementary Information ◽  
Protein Protein Interactions ◽  
Communication Analysis ◽  
Mediate Cell ◽  
Intercellular Communications ◽  
Cell Cell

Abstract Motivation Ligand–receptor (L–R) interactions mediate cell adhesion, recognition and communication and play essential roles in physiological and pathological signaling. With the rapid development of single-cell RNA sequencing (scRNA-seq) technologies, systematically decoding the intercellular communication network involving L–R interactions has become a focus of research. Therefore, construction of a comprehensive, high-confidence and well-organized resource to retrieve L–R interactions in order to study the functional effects of cell–cell communications would be of great value. Results In this study, we developed Cellinker, a platform of literature-supported L–R interactions that play roles in cell–cell communication. We aimed to provide a useful platform for studies on cell–cell communication mediated by L–R interactions. The current version of Cellinker documents over 3700 human and 3200 mouse L–R protein–protein interactions (PPIs) and embeds a practical and convenient webserver with which researchers can decode intercellular communications based on scRNA-seq data. And over 400 endogenous small molecule (sMOL) related L–R interactions were collected as well. Moreover, to help with research on coronavirus (CoV) infection, Cellinker collects information on 16L–R PPIs involved in CoV–human interactions (including 12L–R PPIs involved in SARS-CoV-2 infection). In summary, Cellinker provides a user-friendly interface for querying, browsing and visualizing L–R interactions as well as a practical and convenient web tool for inferring intercellular communications based on scRNA-seq data. We believe this platform could promote intercellular communication research and accelerate the development of related algorithms for scRNA-seq studies. Availability and implementation Cellinker is available at http://www.rna-society.org/cellinker/ Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Analysis of Single-Cell RNA-Seq Identifies Cell-Cell Communication Associated with Tumor Characteristics

Cell Reports ◽  
2018 ◽  
Vol 25 (6) ◽  
pp. 1458-1468.e4 ◽  
Author(s):  
Manu P. Kumar ◽  
Jinyan Du ◽  
Georgia Lagoudas ◽  
Yang Jiao ◽  
Andrew Sawyer ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Communication ◽  
Tumor Characteristics ◽  
Rna Seq ◽  
Cell Cell

Single-Cell Analysis of Cell-Cell Communication of Exosome Components Derived from Melanoma Cells

2020 ◽  
Vol MA2020-02 (44) ◽  
pp. 2825-2825
Author(s):  
Miyu Fukaya ◽  
Tomohiro Hatakenaka ◽  
Nahoko Matsuki ◽  
Seiya Minagawa ◽  
Mikako Saito
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Communication ◽  
Melanoma Cells ◽  
Cell Analysis ◽  
Cell Cell

scholarly journals Myosin-dependent cell-cell communication controls synchronicity of division in acute and chronic stages of Toxoplasma gondii

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Karine Frénal ◽  
Damien Jacot ◽  
Pierre-Mehdi Hammoudi ◽  
Arnault Graindorge ◽  
Bohumil Maco ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Cell Communication ◽  
Dependent Cell ◽  
Cell Cell

scholarly journals A Critical-like Collective State Leads to Long-range Cell Communication in Dictyostelium discoideum Aggregation

2016 ◽  
Author(s):  
Giovanna De Palo ◽  
Darvin Yi ◽  
Robert G. Endres
Keyword(s):  
Single Cell ◽  
Dictyostelium Discoideum ◽  
Long Range ◽  
Early Development ◽  
Cell Communication ◽  
Multiscale Model ◽  
Wild Type ◽  
Social Amoeba ◽  
Range Cell ◽  
Cell Cell

AbstractThe transition from single-cell to multicellular behavior is important in early development but rarely studied. The starvation-induced aggregation of the social amoeba Dictyostelium discoideum into a multicellular slug is known to result from single-cell chemotaxis towards emitted pulses of cyclic adenosine monophosphate (cAMP). However, how exactly do transient short-range chemical gradients lead to coherent collective movement at a macroscopic scale? Here, we developed a multiscale model verified by quantitative microscopy to describe wide-ranging behaviors from chemotaxis and excitability of individual cells to aggregation of thousands of cells. To better understand the mechanism of long-range cell-cell communication and hence aggregation, we analyzed cell-cell correlations, showing evidence of self-organization at the onset of aggregation (as opposed to following a leader cell). Surprisingly, cell collectives, despite their finite size, show features of criticality known from phase transitions in physical systems. By comparing wild-type and mutant cells with impaired aggregation, we found the longest cellcell communication distance in wild-type cells, suggesting that criticality provides an adaptive advantage and optimally sized aggregates for the dispersal of spores.Author SummaryCells are often coupled to each other in cell collectives, such as aggregates during early development, tissues in the developed organism, and tumors in disease. How do cells communicate over macroscopic distances much larger than the typical cell-cell distance to decide how they should behave? Here, we developed a multiscale model of social amoeba, spanning behavior from individuals to thousands of cells. We show that local cell-cell coupling via secreted chemicals may be tuned to a critical value, resulting in emergent long-range communication and heightened sensitivity. Hence, these aggregates are remarkably similar to bacterial biofilms and neuronal networks, all communicating in a pulse-like fashion. Similar organizing principles may also aid our understanding of the remarkable robustness in cancer development.

Fluorescence resonance energy transfer in revealing protein–protein interactions in living cells

2021 ◽  
Author(s):  
Sukesh R. Bhaumik
Keyword(s):  
Single Cell ◽  
Protein Interactions ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Living Cells ◽  
Biological Processes ◽  
Protein Protein Interactions ◽  
Functional Mechanisms

Genes are expressed to proteins for a wide variety of fundamental biological processes at the cellular and organismal levels. However, a protein rarely functions alone, but rather acts through interactions with other proteins to maintain normal cellular and organismal functions. Therefore, it is important to analyze the protein–protein interactions to determine functional mechanisms of proteins, which can also guide to develop therapeutic targets for treatment of diseases caused by altered protein–protein interactions leading to cellular/organismal dysfunctions. There is a large number of methodologies to study protein interactions in vitro, in vivo and in silico, which led to the development of many protein interaction databases, and thus, have enriched our knowledge about protein–protein interactions and functions. However, many of these interactions were identified in vitro, but need to be verified/validated in living cells. Furthermore, it is unclear whether these interactions are direct or mediated via other proteins. Moreover, these interactions are representative of cell- and time-average, but not a single cell in real time. Therefore, it is crucial to detect direct protein–protein interactions in a single cell during biological processes in vivo, towards understanding the functional mechanisms of proteins in living cells. Importantly, a fluorescence resonance energy transfer (FRET)-based methodology has emerged as a powerful technique to decipher direct protein–protein interactions at a single cell resolution in living cells, which is briefly described in a limited available space in this mini-review.

scholarly journals Novel Roles in Human MD-2 of Phenylalanines 121 and 126 and Tyrosine 131 in Activation of Toll-like Receptor 4 by Endotoxin

2007 ◽  
Vol 283 (3) ◽  
pp. 1257-1266 ◽  
Author(s):  
Athmane Teghanemt ◽  
Fabio Re ◽  
Polonca Prohinar ◽  
Richard Widstrom ◽  
Theresa L. Gioannini ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Cell Activation ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Protein Protein Interactions ◽  
Lipopolysaccharide Binding Protein ◽  
Toll Like Receptor 4 ◽  
Dependent Cell ◽  
Cellular Responsiveness ◽  
Tlr4 Activation

Potent mammalian cell activation by Gram-negative bacterial endotoxin requires sequential protein-endotoxin and protein-protein interactions involving lipopolysaccharide-binding protein, CD14, MD-2, and Toll-like receptor 4 (TLR4). TLR4 activation requires simultaneous binding of MD-2 to endotoxin (E) and the ectodomain of TLR4. We now describe mutants of recombinant human MD-2 that bind TLR4 and react with E·CD14 but do not support cellular responsiveness to endotoxin. The mutants F121A/K122A MD-2 and Y131A/K132A MD-2 react with E·CD14 only when co-expressed with TLR4. Single mutants K122A and K132A each react with E·CD14 ± TLR4 and promote TLR4-dependent cell activation by endotoxin suggesting that Phe121 and Tyr131 are needed for TLR4-independent transfer of endotoxin from CD14 to MD-2 and also needed for TLR4 activation by bound E·MD-2. The mutant F126A MD-2 reacts as well as wild-type MD-2 with E·CD14 ± TLR4. E·MD-2F126A binds TLR4 with high affinity (Kd ∼ 200 pm) but does not activate TLR4 and instead acts as a potent TLR4 antagonist, inhibiting activation of HEK/TLR4 cells by wild-type E·MD-2. These findings reveal roles of Phe121 and Tyr131 in TLR4-independent interactions of human MD-2 with E·CD14 and, together with Phe126, in activation of TLR4 by bound E·MD-2. These findings strongly suggest that the structural properties of E·MD-2, not E alone, determine agonist or antagonist effects on TLR4.

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