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K.Muma Bio 6 Cell Communication Study Objectives: 1. Describe the different mechanisms of cell communication: direct contact vs. extracellular messengers. 2. Compare and contrast paracrine, autocrine, neurotransmitters, hormonal, and neurohormonal communication. 3. Discuss the general mechanism of hormone action and list the effects they can have on cellular activity 4. Distinguish between lipid soluble and water soluble hormones. Describe how they are transported in the blood and the type of receptors they bind to at the target cells. 5. Define and give examples of secondary messengers. 6. Describe the general mechanism of the cyclic AMP signal transduction pathway. 7. Describe the general mechanism of the calcium signal transduction pathway. Cell Communication Outline I. Types of Cellular Communication (See figure 4-20) a. Direct contact between cells i. Gap junctions – cells are connected by tunnels formed by connexons 1. Allows ions and small water soluble chemicals to pass between cells 2. Examples: cardiac and smooth muscle ii. Cell to cell recognition – interaction of cell-surface molecules 1. Example: immune cells – recognize self vs. non-self b. Through extracellular chemical messengers - cells release ligands that bind to receptors on target cells to initiate a desired cellular response i. Local regulators 1. Paracrine – through diffusion, ligands affect cells in the local vicinity a. Examples: histamine, cytokines, prostaglandins 2. Autocrine – chemicals act on the cell that produced it 3. Neurotransmitters – secreted by neurons a. Diffuse across the synaptic cleft and target the adjacent cell (neuron, gland, muscle) b. Short-lived ii. Long-range (distant) regulators 1. Hormones – secreted into the blood by endocrine glands to travel to distant target cells 2. Neurohormones – neurons secretes hormones into the blood II. Cellular Effects of Chemical Signals a. Example of various effects chemical signals may have on the target cell i. Activate or inhibit enzymes ii. Direct protein synthesis through activation of transcription factors iii. Stimulate cell division iv. Alter membrane permeability – membrane potential or opening/closing of ion channels b. How do hormones work? i. Hormones are chemical substances that travel through the blood to a target cell ii. Target cells must have specific receptors to which the hormone binds iii. These receptors may be intracellular or located on the plasma membrane iv. They trigger a change in cellular activity c. Types of Hormones/Chemical Signals i. Amines – amino acid derivatives 1. Examples: catecholamines (NE and E), T3, T4, serotonin, melatonin ii. Peptides – proteins 1. Examples: vasopressin (ADH), insulin iii. Steroids – cholesterol based 1. Examples: cortisol, aldosterone, estrogen, testosterone iv. Eicosanoids –derived from arachidonic acid 1. Prostaglandins, leukotrienes d. Transport of Hormones i. Hydrophilic (water-soluble) hormones – transported dissolved in the plasma 1. Examples: peptide and catecholamines ii. Lipophilic (lipid-soluble) hormones – circulate bound to plasma proteins such as albumin 1. Examples: steroids and thyroid hormones e. Mechanism of Signaling Molecules i. Lipid soluble hormones (see figure 4-28) 1. Move through the plasma membrane and bind to an intracellular receptor in the nucleus 2. Binding of the hormone receptor complex to the DNA triggers transcription of a specific gene and the synthesis of a protein that initiates a cellular response ii. Water soluble hormones- utilize a membrane bound receptor 1. Binding of hormone causes a conformational change in the receptor 2. Affects of ligands binding to membrane bound receptors (see figure 4-22): a. Triggers the opening or closing of ion channels OR b. Transfers the signal to a secondary messenger within the cell which triggers a cascade of biochemical events III. Signal Transduction a. Secondary Messenger Pathways i. Signaling pathways amplify the cells response to signals ii. G-protein linked receptor – spans the membrane and is associated with a G protein on the cytoplasmic side (see figure 422c) 1. Ligand binds to the receptor 2. Receptor then activates a G protein iii. G proteins are considered relay proteins that cycle between an inactive and active form b. Types of secondary messenger pathways i. Cyclic AMP Secondary Messenger Pathway (see figure 4-25) 1. G protein activates the enzyme adenylyl cyclase (the effector) 2. Converts ATP to cyclic AMP 3. Activates protein kinase A which phosphorylates other proteins 4. Trigger cellular responses ii. Calcium Secondary Messenger Pathway (see figure 4-26) 1. Binding of extracellular messenger to a G protein linked receptor or a tyrosine kinase receptor 2. Activates phospholipase C which converts PIP2 to DAG and IP3 3. DAG will activate protein kinase C in another signaling pathway 4. IP3 binds to calcium channels triggering the release of calcium from the ER into the cytoplasm 5. Calcium binds to and activates calmodulin which can alter other proteins to bring about a cellular response Post-lecture Practice 1. When a ligand triggers a secondary messenger pathway a cascade of events occurs. Place the following events of the calcium signaling pathway in the proper sequence 1 being the first event and 9 being the last. _____ IP3 binds to an IP3 receptor on the smooth endoplasmic reticulum _____ G-protein is activated _____ the effector phospolipase C is activated _____ ligand binds to G-linked protein receptor _____ calcium is released from the smooth ER and dumped into the cytosol _____ transcription factors are activated _____ cellular response occurs _____calcium activates calmodulin _____ PIP2 is converted into DAG and IP3 2. Categorize the following signaling molecules as local regulators or distant regulators: Chemical signaling through gap junctions Paracrine Neurotransmitters Hormones Neurohormones Cell to cell recognition Autocrine