Cell Communication Dr Safa Abdul Ghani Overview of Cell to Cell Communication: • Two basic types of physiological signals: I. Electrical : changes in a cell s membrane potential II. Chemical : molecules secreted by cells into the extracellular Fluid. Chemical signals are responsible for most communication within the body. The cells that receive electrical or chemical signals are called target cells • Chemical • Autocrine & Paracrine: Local Signaling • Endocrine system: Distant, Diffuse Target • Electrical • Gap Junction: Local • Nervous System: Fast, Specific, Distant Target four basic methods of cell-to-cell communication: (1) gap junctions, which allow direct cytoplasmic transfer of electrical and chemical signals between adjacent cells (2) contact-dependent signals, which occur when surface molecules on one cell membrane bind to surface molecules on another cells membrane (3) local communication by chemicals that diffuse through the extracellular fluid (4) long-distance communication through a combination of electrical signals carried by nerve cells and chemical signals transported in the blood 1) Gap Junctions Protein channels – connexin Direct flow to neighbor - Electrical-ions (charge) - Signal chemicals 2) Contact dependent signal CAMs (Cell adhesion molecules) - Need direct surface contact - Signal chemical Direct and local cell-to-cell communication 3)Paracrines and Autocrines (Local communication) • Local communication • Signal chemicals diffuse to target • Example: Cytokines - Autocrine receptor on same cell - Paracrine receptor on neighboring cells Direct and local cell-to-cell communication 4)Long Distance Communication: Hormones • Signal Chemicals • Made in Endocrine Cells • Transported via Blood • Receptors on Target Cells Figure 6-2a: Long distance cell-to-cell communication 4) Long Distance Communication: Neurons and Neurohormones • Neurons Electrical Signal down Axon Signal Molecule (Neurotransmitter) to Target Cell • Neurohormones Chemical and Electrical Signals down Axon Hormone Transported via Blood to Target Figure 6-2 b: Long distance cell-to-cell communication Long Distance Communication: Neurons and Neurohormones Figure 6-2 - Overview Signal Pathways • Signal Molecule (Ligand) • Receptor • Intracellular Signal • Target Protein • Response Receptor locations Cytosolic or Nuclear - Lipophilic ligand enters cell - Often activates gene - Slower response Cell Membrane - Lipophobic Ligand can't enter cell - Outer Surface Receptor - Fast Response Figure 6-4: Target cell receptors Figure 6-4 (3 of 3) Membrane Receptor Classes • Ligand- Gated Channel (Receptor Channel) • Receptor Enzymes • G-Protein-Coupled • Integrin Figure 6-5 Membrane Receptor Classes Figure 6-5: Four classes of membrane receptors Signal Transduction Transforms Signal Energy Protein Kinase Second Messenger Activate Proteins • Phosporylation • Bind Calcium Cell Response Figure 6-8: Biological signal transduction Figure 6-6 Figure 6-7 Figure 6-8 Table 6-1 Table 6-2 Figure 6-9 Receptor Enzymes Transduction Activation Cytoplasmic - Side Enzyme Example: Tyrosine Kinase Figure 6-10: Tyrosine kinase, an example of a receptor-enzyme G-Protein-Coupled Receptors Hundreds of Types Main Signal Transducers • Activate Enzymes • Open Ion Channels • Amplify: Adenyl Cyclase-cAMP • Activates Synthesis G-Protein-coupled Receptors Figure 6-11 - Overview Figure 6-11, step 1 Figure 6-11, step 2 Figure 6-11, step 3 Figure 6-11, step 4 Figure 6-11, step 5 Figure 6-12 - Overview Figure 6-12, step 1 Figure 6-12, step 2 Figure 6-12, step 3 Figure 6-12, step 4 Figure 6-12, step 5 Figure 6-5 RECEPTOR CHANNELS Figure 6-13 Figure 6-14 Novel Signal Molecules Calcium: - Channel Opening - Muscle Contraction - Enzyme Activation - Vesicle Excytosis Nitric Oxide (NO) - Paracrine: Arterioles - Activates cGMP - Brain Neurotransmitter Modulation of Signal Pathways by Ligands Multiple Ligands Agonist Turn on Receptor Antagonist Block Receptor Activity Figure 6-17: Agonists and antagonists Modulation by Receptors Multiple Receptors for a Ligand: Epinephrine (adrenaline) • Alpha Receptor / Vasoconstriction • Beta Receptor / Vasodilation Receptor Up-Regulation: Grow More Receptors Receptor Down-Regulation: Grow Fewer Receptor • Excess Stimulation • Drug Tolerance Endocytosis of Ligand & Receptor Modulation by Receptors Figure 6-18: Target response depends on the target receptor Homeostasis and “Homeodynamic” • Cannon's Postulates (Concepts) • Nervous Regulation of Internal Environment (control blood volume, blood osmolarity, blood pressure, and body temperature) • Tonic Level of Activity (Blood vessel diameter) • Antagonistic Controls (ex. insulin and glucagon) • Chemical Signals can have Different Effects on Different Tissues Figure 6-19 Tonic Level of Activity (Blood vessel diameter) Figure 6-20 Antagonistic Controls Figure 6-21 - Overview Figure 6-21a Figure 6-21b Control Pathways ā®Maintain Homeostasis Local–Paracrines (ex.Nitric oxide) Long-Distance–Reflex Control • Nervous • Endocrine • Cytokines Control Pathways Figure 6-22 Reflex Control Stimulus Sensory Receptor Afferent Path Integration Center Efferent Path Effector- Target Cell/Tissue Response (Feedback Loop) Figure 6-22: Steps of a reflex Types of Receptors: Membrane, CNS & Peripheral Figure 6-23: Multiple meanings of the word receptor Feedback Loops • Negative Feedback: Are Homeostatic Response Slows Stimulation Return to Optimal Range • Positive Feedback: Stimulation Drives more Stimulation • Feed Forward: Prepares Body for Change Feedback Loops Are Not Homeostatic : Negative and positive feedback Feedback Loops Figure 6-28 Complexity and Modulation of Control Systems Specificity Nature of Signal Speed Duration Stimulation Intensity Figure 6-30a Figure 6-30b Figure 6-30c Table 6-4 Figure 6-31 - Overview Figure 6-31, step 1 Figure 6-31, step 2 Figure 6-31, step 3 Figure 6-31, step 4 Figure 6-31, step 5 Figure 6-31, step 6 Table 6-5 Summary Integration of Systems uses: Local, Endocrine and Nervous Communications Signals Travel Via: Diffusion, Gap Junctions, Axons, and Blood to Target Cells Receptor Types and Functions: Binding, Transduction, Amplification, Activation, Cell Responses Receptors are Modulated by: Competition, Specificity, Blocking, Up– and Down–Regulation Concepts of Homeostasis (Homeodynamics) Reflex Control Pathways, Types, Feedback and their Regulation