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Physiological Reviews Jul 2021G protein-coupled receptors (GPCRs) regulate many cellular and physiological processes, responding to a diverse range of extracellular stimuli including hormones,... (Review)
Review
G protein-coupled receptors (GPCRs) regulate many cellular and physiological processes, responding to a diverse range of extracellular stimuli including hormones, neurotransmitters, odorants, and light. Decades of biochemical and pharmacological studies have provided fundamental insights into the mechanisms of GPCR signaling. Thanks to recent advances in structural biology, we now possess an atomistic understanding of receptor activation and G protein coupling. However, how GPCRs and G proteins interact in living cells to confer signaling efficiency and specificity remains insufficiently understood. The development of advanced optical methods, including single-molecule microscopy, has provided the means to study receptors and G proteins in living cells with unprecedented spatio-temporal resolution. The results of these studies reveal an unexpected level of complexity, whereby GPCRs undergo transient interactions among themselves as well as with G proteins and structural elements of the plasma membrane to form short-lived signaling nanodomains that likely confer both rapidity and specificity to GPCR signaling. These findings may provide new strategies to pharmaceutically modulate GPCR function, which might eventually pave the way to innovative drugs for common diseases such as diabetes or heart failure.
Topics: Animals; Cell Membrane; GTP-Binding Proteins; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 33331229
DOI: 10.1152/physrev.00021.2020 -
Frontiers in Immunology 2019The nuclear factor-κB (NF-κB) signaling pathway is one of the best understood immune-related pathways thanks to almost four decades of intense research. NF-κB... (Review)
Review
The nuclear factor-κB (NF-κB) signaling pathway is one of the best understood immune-related pathways thanks to almost four decades of intense research. NF-κB signaling is activated by numerous discrete stimuli and is a master regulator of the inflammatory response to pathogens and cancerous cells, as well as a key regulator of autoimmune diseases. In this regard, the role of NF-κB signaling in immunity is not unlike that of the macrophage. The dynamics by which NF-κB proteins shuttle between the cytoplasm and the nucleus to initiate transcription have been studied rigorously in fibroblasts and other non-hematopoietic cells, but many questions remain as to how current models of NF-κB signaling and dynamics can be translated to innate immune cells such as macrophages. In this review, we will present recent research on the dynamics of NF-κB signaling and focus especially on how these dynamics vary in different cell types, while discussing why these characteristics may be important. We will end by looking ahead to how new techniques and technologies should allow us to analyze these signaling processes with greater clarity, bringing us closer to a more complete understanding of inflammatory transcription factor dynamics and how different cellular contexts might allow for appropriate control of innate immune responses.
Topics: Animals; Humans; Immunity, Innate; Inflammation; Macrophages; NF-kappa B; Signal Transduction
PubMed: 31024544
DOI: 10.3389/fimmu.2019.00705 -
International Journal of Molecular... Aug 2021Neurodegenerative diseases are characterized by the progressive loss of specific subsets of neurons [...].
Neurodegenerative diseases are characterized by the progressive loss of specific subsets of neurons [...].
Topics: Animals; Cell Communication; Humans; Neurodegenerative Diseases; Neurons; Signal Transduction
PubMed: 34445683
DOI: 10.3390/ijms22168978 -
Science (New York, N.Y.) Jul 2018A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch...
A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multidomain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: Signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.
Topics: Artificial Cells; Cell Adhesion; Cell Communication; Cell Engineering; Cells; Morphogenesis; Signal Transduction; Spheroids, Cellular
PubMed: 29853554
DOI: 10.1126/science.aat0271 -
Experimental Cell Research Sep 2017Endothelial cells line blood vessels and provide a dynamic interface between the blood and tissues. They remodel to allow leukocytes, fluid and small molecules to enter... (Review)
Review
Endothelial cells line blood vessels and provide a dynamic interface between the blood and tissues. They remodel to allow leukocytes, fluid and small molecules to enter tissues during inflammation and infections. Here we compare the signaling networks that contribute to endothelial permeability and leukocyte transendothelial migration, focusing particularly on signals mediated by small GTPases that regulate cell adhesion and the actin cytoskeleton. Rho and Rap GTPase signaling is important for both processes, but they differ in that signals are activated locally under leukocytes, whereas endothelial permeability is a wider event that affects the whole cell. Some molecules play a unique role in one of the two processes, and could therefore be targeted to selectively alter either endothelial permeability or leukocyte transendothelial migration.
Topics: Actins; Adherens Junctions; Animals; Cell Adhesion; Endothelial Cells; Humans; Leukocytes; Signal Transduction
PubMed: 28602626
DOI: 10.1016/j.yexcr.2017.06.003 -
Cells Feb 2023Autoreactive B cells play a key role in the initiation or aggravation of many systemic and tissue-specific autoimmune disorders [...].
Autoreactive B cells play a key role in the initiation or aggravation of many systemic and tissue-specific autoimmune disorders [...].
Topics: Humans; Autoimmunity; Autoimmune Diseases; B-Lymphocytes; Signal Transduction
PubMed: 36766841
DOI: 10.3390/cells12030499 -
Biomedical Journal Apr 2022This special edition summarizes major advances in our understanding of signaling by T lymphocytes. T cell interactions with antigen-presenting cells (APCs) and other...
This special edition summarizes major advances in our understanding of signaling by T lymphocytes. T cell interactions with antigen-presenting cells (APCs) and other immune cells are characterized by changes in T cell adhesion and major rearrangements of the actin cytoskeleton. This issue describes some of the mediators of these changes both within the T cells and on the T cell surface. The five articles focus on "inside-out integrin signaling" in T cells, components of the immunological synapse between lymphocyte and APCs, an unexpected role for T cell receptor (TCR) signaling from endosomes, transfer of membrane constituents from APCs to T cells via trogocytosis, immune deficiencies in these T cell signaling pathways, and the role of thymocyte-expressed molecule involved in selection (THEMIS) in thymocyte development and peripheral T cell function.
Topics: Humans; Immunological Synapses; Lymphocyte Activation; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes
PubMed: 35430421
DOI: 10.1016/j.bj.2022.04.002 -
ChemistryOpen Jun 2020Communication between and inside cells as well as their response to external stimuli relies on elaborated systems of signal transduction. They all require a directional... (Review)
Review
Communication between and inside cells as well as their response to external stimuli relies on elaborated systems of signal transduction. They all require a directional transmission across membranes, often realized by primary messenger docking onto external receptor units and subsequent internalization of the signal in form of a released second messenger. This in turn starts a cascade of events which ultimately control all functions of the living cell. Although signal transduction is a fundamental biological process realized by supramolecular recognition and multiplication events with small molecules, chemists have just begun to invent artificial models which allow to study the underlying rules, and one day perhaps to rescue damaged transduction systems in nature. This review summarizes the exciting pioneering efforts of chemists to create simple models for the basic principles of signal transduction across a membrane. It starts with first attempts to establish molecular recognition events on liposomes with embedded receptor amphiphiles and moves on to simple transmembrane signaling across lipid bilayers. More elaborated systems step by step incorporate more elements of cell signaling, such as primary and secondary messenger or a useful cellular response such as cargo release.
Topics: Biomimetics; Cell Membrane; Humans; Models, Biological; Signal Transduction
PubMed: 32699734
DOI: 10.1002/open.201900367 -
Cells Oct 2022Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional... (Review)
Review
Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional studies in B cells from patients or specific animal models and by the observed efficacy of small-molecule inhibitors. In this review, we first discuss key signal transduction pathways downstream of the B cell receptor (BCR) that ensure that autoreactive B cells are removed from the repertoire or functionally silenced. We provide an overview of aberrant BCR signaling that is associated with inappropriate B cell repertoire selection and activation or survival of peripheral B cell populations and plasma cells, finally leading to autoantibody formation. Next to BCR signaling, abnormalities in other signal transduction pathways have been implicated in autoimmune disease. These include reduced activity of several phosphates that are downstream of co-inhibitory receptors on B cells and increased levels of BAFF and APRIL, which support survival of B cells and plasma cells. Importantly, pathogenic synergy of the BCR and Toll-like receptors (TLR), which can be activated by endogenous ligands, such as self-nucleic acids, has been shown to enhance autoimmunity. Finally, we will briefly discuss therapeutic strategies for autoimmune disease based on interfering with signal transduction in B cells.
Topics: Animals; Receptors, Antigen, B-Cell; B-Lymphocytes; Signal Transduction; Autoimmune Diseases; Toll-Like Receptors
PubMed: 36359789
DOI: 10.3390/cells11213391 -
American Journal of Physiology. Cell... Feb 2015
Topics: Animals; Cell Communication; Cell Membrane; Humans; Membrane Proteins; Signal Transduction
PubMed: 25640038
DOI: 10.1152/ajpcell.7685-editorial.2015