Cell‒Cell Communication in Health and Disease

communication in & Cells use a variety of mechanisms to transmit essential information, facilitating their growth, response and survival. Each form of communication is vital for maintaining correct biological functions and microenvironmental homeostasis of cells, tissues and organ systems. But sometimes, Miscommunication between cells can interfere with things go crucial signaling processes, potentially causing disease. wrong... By understanding these pathways and pinpointing the source of miscommunication, we can improve the management and treatment of disease. In this infographic, we explore the general principles of cell communication and highlight the relationship between signaling defects and disease. Types of cell communication 1 Endocrine Signaling Signaling cell signals originate from distant cells known as endocrine cells. Mechanism Characteristics Hormones, the signaling molecules in Produces slower Bloodstream endocrine signaling, move through the but longer-lasting bloodstream to distant target cells. responses. Target cell Example Insulin release to regulate blood sugar levels. 2 Paracrine Signaling signals target neighboring cells near the signaling cell. Presynaptic neuron Mechanism Characteristics Signaling molecules travel a Localized signaling short distance through the triggers rapid extracellular matrix to reach responses that are a target cell. short-lived. Neurotransmitters Axon terminal Example Synaptic Transfer of neurotransmitters across a synaptic gap vesicles between nerve cells. Synaptic cleft Ligand-gated channels with receptors for neurotransmitters Postsynaptic neuron Target cell Signaling cell 3 Autocrine Signaling cells produce and respond to their own signals, essentially signaling to themselves. Mechanism Characteristics Ligands released by a Common in early development for cell bind to receptors on tissue differentiation, regulation of pain, the same cell or similar inflammatory responses and programmed nearby cells. cell death in diseased/infected cells. Example Immune cells release cytokines that act on the same cell to amplify a particular immune response. 4 Direct Signaling Also known as juxtacrine signaling signals are transferred through direct contact between cells via membrane proteins or specialized channels. Mechanism Characteristics Signals are transmitted along Allows for the cell membranes via protein or quick transfer of Gap Junction lipid components integral to the signals across cells, cell’s membrane. They can impact enabling coordinated the signaling cell itself or cells responses. that are directly adjacent to the signaling cell. connexon2 connexon1 Example Electrical signals pass between cardiomyocytes through gap junctions. A closer look at signal transmission via gap junctions… Signaling molecules diffuse from Connexin-based gap junction channels one cell to another via tiny channels are composed of two hemichannels, called gap junctions, facilitating (connexons) each provided by one of rapid communication. Th the two neighboring cells, creating a gap specificity of channel sizes blocks junction to allow passage of ions, second the transfer of very large molecules messengers and small metabolites via (e.g., proteins). the cytoplasm. Cell signaling steps 1 2 Signaling Reception signals originate from The signaling molecule distant cells known as binds to the target cell endocrine cells. via a receptor. 3 4 Transduction Response The signal is transmitted The signal triggers a physiologically via a cascade of appropriate change in the cell (e.g., intracellular events. gene expression, enzyme activity) 5 Termination The cell signaling cascade is terminated to prevent inappropriate activity. Signal transduction pathways aren’t always linear, they can involve: Convergence Signals from various unrelated receptors converge to activate shared effector molecules. Divergence A single receptor initiates multiple effector pathways. Crosstalk Interactions between different signaling pathways amplify or reduce other signals. When communication goes wrong Alterations in cell–cell communication – by hyperactivation or diminished signaling – can stop cells from responding to standard cues or coordinating with other cells appropriately, leading to disease. Let's take a look at a few examples… Diabetes Sugar Insulin Type I diabetes is classed as a T-cell-driven autoimmune disease that results in the destruction and/or dysregulation of insulin ß producing ß cells in the pancreas. Insulin production is compromised, leading to high blood sugar levels. In Type II diabetes, Type I Diabetes Type II Diabetes cells ignore insulin's effects, causing similar No insulin signal No response sugar imbalances. Multiple Sclerosis (MS) MS destroys the protective myelin sheath Nerve cell with sclerosis (demyelination) that usually insulates the axon, disrupting signal transmission along the nerve. This leads to symptoms like Muscle unable muscle weakness and vision problems. to contract Ischemic Stroke and Excitotoxicity Post-stroke, dying brain cells release glutamate excessively, damaging or killing unaffecte Normal veins neighboring cells. A stroke-induced deficit in glucose and oxygen disrupts oxidative phosphorylation, which forces open voltage-gated calcium channels and Anoxia leads to ionic imbalance. This causes an influ Thrombu of calcium ions into the neuron, triggering the release of more glutamate into the synapse which A clot blocks then associates with the postsynaptic neuron, blood flow to an destroying it. area of the brain As each neuron dies, more glutamate is released, overstimulating and killing the surrounding cells. Cancer Multiple failures in cell signaling can lead to unchecked cell growth and cancer. For example, cancer cells can manipulate their blood supply either directly, by emitting pro-angiogenic signals, or indirectly, by inducing adjacent cells to release these signals for them. Hypoxia inducible factor and vascular endothelial growth factor signaling pathways are both Angiogenesis integral to tumor angiogenesis. In early-stage cancers, transforming ß growth factor (TGF)-ß signaling can inhibit cancer cell growth and promote apoptosis. However, resistance can occur through acquired mutations – either in genes within -ß the TGF-ß pathway itself, or in some of its target genes. Pinpointing the source of miscommunication Identifying specific signaling defects and analyzing cell–cell communication in the laboratory can involve a range of techniques, for example… Western Blotting Used to detect specific proteins involved in signaling pathways and to assess their levels of expression or activation through post-translational modifications Flow Cytometry Used to analyze the expression of cell surface and intracellular signaling molecules, providing insights into cellular function and signaling status. It can also be used to sort cells based on certain characteristics. RT-qPCR Used to determine mRNA levels of genes involved in signaling pathways, providing insight into how signaling might change gene expression. Mass Spectrometry Used to identify and quantify signaling proteins and their modifications providing a detailed view of the cell signaling network. Live-Cell Imaging Used to track signaling processes in living cells, in real time. This allows researchers to observe how cells respond to stimuli over a specific period and the transduction events within cells and signaling between cells. Patch-Clamp Used to measure how electrical signals affect molecular ion channel behavior in real time. This helps researchers understand electrical signaling in various cell types including neurons, cardiomyocytes, oocytes and muscle cells. Single-Cell RNA Sequencing and Spatial Transcriptomics Used to understand complex cellular environments. Single-cell RNA sequencing provides insights into the transcriptomic profile of individual cells or cell clusters, within a mixed population. This granularity enables the mapping of cell signaling pathways and the interactions that drive cellular functions and behaviors. Spatial transcriptomics adds further context by revealing the spatial arrangement of cells.