Topic 1 Principle of Cell Signalling (Part I) PDF

Topic 1 Principle of Cell Signalling (Part I) BIOL 2036SEF / S236F Cellular and Molecular Biology 2 Topic Covered ▪ ▪ Readings: Chapter 9, Biology Principles of Cell Signalling Receptors and Signalling Molecules ▪ ▪ Signalling Pathway Tools and Techniques for Cell Signalling Studies Principles of Ce...

Topic 1 Principle of Cell Signalling (Part I) BIOL 2036SEF / S236F Cellular and Molecular Biology 2 Topic Covered ▪ ▪ Readings: Chapter 9, Biology Principles of Cell Signalling Receptors and Signalling Molecules ▪ ▪ Signalling Pathway Tools and Techniques for Cell Signalling Studies Principles of Cell Signalling 4 Overview 5 What’s Cell Signalling ▪ Communication between different cells ▫ Quorum sensing (群聚感應)(coordination between bacteria) ▫ Coordination in development and function ▪ The intracellular event of a cell in response to external and internal changes ▪ Signal  receptor  pathway response Feedback and Regulation 6 What’s Cell Signalling Upstream ▪ Why can we draw this principle? Downstream Not exhaustive Molecular Biology of the Cell 6th Edition regulate cell proliferation, differentiation, and death Signalling Cascade 7 Autocrine Types of Signalling ▪ What are the differences? Molecular Biology of the Cell 6th Edition Extracellular fluid Embryo development / Immune response Immune response Nerve impulse Growth / Metabolism 8 9 Types of Signalling Distance Types of Tissues Duration of the Signal (molecules) Short /long Same Tissues Transient Muscle contraction Short Between different cells types Seconds Immune response Endocrine Long Different tissues / organs Hours Hormones Synaptic Long/ Between Synapse Between two nerve cells Milliseconds Nerve impulse Direct Contact Paracrine Examples 10 Common Features of Cell Signalling 11 ▪ Signaling is initiated by specific binding Signalling is Initiated by Specific Binding between ligands (signal) and receptor ▪ Usually between two cells or more ▪ Signal released by exocytosis, direct diffusion, or on cell surface ▪ Similar to enzyme and substrate binding  high-specificity ▪ High affinity binding due to low concentration of ligands (10-8M) Same signal molecules, Different Responses. Why? Molecular Biology of the Cell 6th Edition 12 13 ▪ The transduction process is unique to each The Response is Cell-Type Dependent cell type, to respond to a signal, different cells require only a similar membrane receptor. ▪ Effect of a signalling molecules is cell-type dependent ▪ Different cells are programmed to respond differently ▪ The complexity lies within the difference in the intracellular signalling proteins, effectors proteins, and gene activated ▪ The signal itself carries little information 14 Cellular Response is the Result of Combination of Signals ▪ Cells receives multiple signals ▪ Cell respond by integrating all the signals Molecular Biology of the Cell 6th Edition 15 Receptors are Classified into Cell Surface Receptor and Intracellular Receptor ▪ Hydrophilic signalling molecules ▪ Hydrophobic, small signalling molecules Molecular Biology of the Cell 6th Edition 16 They play an important role in the transmission of neuronal signals at the synapses and the neuromuscular junctions There are Three Types of CellSurface Receptor ▪ Ion-channel-coupled receptor ▪ G-protein-coupled receptor ▪ Enzyme-coupled receptor Neurotransmitter binds  Ion channels opens  Ions moves through channel, across cell membrane Molecular Biology of the Cell 6th Edition 17 GPCRs are involved in a wide variety of physiological processes. Behavioral and mood regulation: Receptors in the brain bind several different neurotransmitters, including serotonin, histamine GABA and glutamate Autonomic nervous system transmission: Both the sympathetic and parasympathetic nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, and digestive processes = catalytic receptor 18 Autophosphorylation Protein Kinase Docking The binding of an extracellular ligand causes enzymatic activity on the intracellular side Examples of the enzymatic activity include: Receptor tyrosine kinase, as in fibroblast growth factor receptor. Most enzyme-linked receptors are of this type. Serine/threonine-specific protein kinase, as in bone morphogenetic protein Guanylate cyclase, as in atrial natriuretic factor receptor Molecular Biology of the Cell 6th Edition 19 There are Three Types of CellSurface Receptor ▪ Ion-channel-coupled receptor ▪ Enzyme-coupled receptor ▪ G-protein-coupled receptor There are Three Types of CellSurface Receptor ▪ Ion-channel-coupled receptor ▪ Enzyme-coupled receptor ▪ G-protein-coupled receptor ▪ Ion-channel-coupled receptor ▫ Nerve / muscle ion channel ▪ Enzyme-coupled receptor ▫ Coupled with enzyme ▪ G-protein-coupled receptor ▫ Trimeric GTP-binding protein ▫ Activate ion channel or enzyme Intracellular signalling molecules or Secondary messenger Intracellular Receptor Apart from hormone, some immune receptors are also intracellular, such as TLR 3 and TLR 9 21 22 23 24 Cell-Surface Receptor Relay Signal via Intracellular Signalling Molecules ▪ Relay message into the cell interior ▫ Detect and measure the magnitude a specific signal in one location ▫ Generate an appropriately timed and measured signal in another location ▪ Provide specificity and control 25 Cell-Surface Receptor Relay Signal via Intracellular Signalling Molecules ▪ Two types of intracellular signalling molecules ▫ Secondary messengers ▫ cAMP, Ca2+, IP3, diacylglycerol ▫ Intracellular signalling proteins ▫ Protein kinase (phosphorylation) ▫ Serine/threonine kinase ▫ Tyrosine kinase ▫ GTP-binding proteins Molecular Switch Molecular Biology of the Cell 6th Edition 26 27 Intracellular Signalling is Specific and Precise ▪ Problems ▫ Crisscross of pathways ▫ Noise ▪ Specificity is maintained by ▫ High affinity and specificity ▫ High level of upstream signal ▫ Simultaneous activation of different pathways ▫ Dual signals ▫ Association of related intracellular signalling molecules 28 Intracellular Signalling is Specific and Precise Activation Inhibition Molecular Biology of the Cell 6th Edition 29 Molecular Biology of the Cell 6th Edition 30 Intracellular Signalling is Specific and Precise Molecular Biology of the Cell 6th Edition 31 Intracellular Signalling Molecules are Organised into Complex ▪ Related intracellular signalling molecules are organised around a scaffold protein ▪ Maintain specificity ▪ Increase efficiency 32 Intracellular Signalling Molecules are Organised into Complex Molecular Biology of the Cell 6th Edition 33 Molecular Biology of the Cell 6th Edition 34 Molecular Biology of the Cell 6th Edition 35 Intracellular Signalling Molecules are Organised into Complex ▪ Preformed signaling complex on a scaffold protein ▪ Assembly of signaling complex on an activated receptor ▪ Assembly of signaling complex on phosphoinositide docking sites 36 Regulation of Cell Signalling 37 Regulation of Cell Signalling ▪ Sensitivity to signal ▪ Availability of intracellular signaling molecules ▪ Turnover time of intracellular signalling molecules ▫ Continuous turnover of intracellular signalling molecules ▪ Feedback mechanisms ▪ Responsiveness to signals 38 Desensitisation to Signals Molecular Biology of the Cell 6th Edition Time delay 39 Feedback Signal Persists Signal Persists Signal Lost Signal Lost Equilibrium Molecular Biology of the Cell 6th Edition 40 Due to Positive Feedback Responsiveness ▪ Sigmoidal response provides filtering to noise Gradual Increase ▪ All-or-none responses leads to cell memory ▫ Cell differentiation Molecular Biology of the Cell 6th Edition Sharp increase in response after passing the threshold 41 References ▪ Raven M., Johnson G., Mason K., et al., Chapter 9 – Cell Communication, Biology. 11th Edition. New York: McGraw-Hill Education, 2017 ▪ Albert B., Johnson A., Lewis J., et al., Chapter 15 - Cell Signaling, Molecular Biology of the Cell. 6th Edition. New York: Garland Science; 2015 42 Thanks! Any questions? You can find me at [email protected] & Tel: 27685938