Chapter 11 Cell Communication Cell Signaling Evolved early in the History of Life Communication between mating yeast cells. Yeast cells use chemical signaling Induced changes lead to fusion. The resulting a/a cell is diploid. Local Chemical Signaling Paracrine Secreting cell acts on nearby target cell by discharging molecules into the extracellular fluid Synaptic Nerve cell releases neurotransmitter into synapses Distant Cell Communication Hormones signal target cells at much greater distances. Secreted into the body fluids, they reach all parts of the body. Only specific target cells are recognized and respond Major Glands and their Hormones Growth Hormone Thyroxine Epinephrine (adrenaline) Insulin and Glucagon Testosterone Estrogen Local and Distant Cell Communication In Animals. Cells also communicate by direct contact. 1. Cell Junctions Signaling substances dissolved in the cell can pass freely from one cell to another 2. Direct Contact Through molecules on the surface of the cell (embryonic development and the immune system) Communication by Direct Contact with Cells. The Three Stages of Cell Signaling For a chemical signal to elicit a specific response, the target cell must possess a signaling system for the signal. 1. Reception 2. Transduction 3. Response Overview of Cell Signaling. Reception – signal (ligand) binds to a specific cell surface protein. Transduction – binding results in conformation change of receptor. This initiates transduction (one or many steps) Response – almost any cellular activity • Many signal molecules cannot pass freely through the plasma membrane • Receptors are located on the plasma membrane • These families are called: - G-protein linked receptors - tyrosine kinase receptors - ion channel receptors The Structure of a G-protein –linked Receptor. The Functioning of a G-Protein Linked- Receptor (e.g. epinephrine receptor). • G-proteins bind guanine nucleotides • GDP – inactive state, GTP – active state • Signal binding changes receptor conformation • Interacts with G-protein • G-protein binds GTP • Activated G-protein binds to another protein (enzyme) • Activation of subsequent target. • Activation state is temporary • Critical metabolic and developmental processes • Defects in G-protein signaling form the bases of many human disease states. • Cholera, whooping cough and botulism, due to toxins that interfere with G-protein function. The Structure and Function of a Tyrosine Kinase Receptor. Tyrosine Kinase Receptors • Extracellular ligand-binding domain. • Cytosolic domain with tyrosine kinase (tk) enzyme activity. Ligand binding causes dimerization. Activates endogenous tk activity. Transfer of PO4 from ATP to tyrosine – autophosphorylation. Interaction with other cellular proteins, resulting in activation of relay proteins – many responses Protein phosphatase terminates the signal process A ligand-gated ion-channel receptor. (important in nervous system) Overview Animation Reception 11.2 http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html http://www.wiley.com/college/fob/anim/ http://www.youtube.com/watch?v=3nODx3cT1RU Not All Signal Receptors Are Located on the Plasma Membrane • Some receptors are proteins located in the cytoplasm or nucleus • The signal molecules for these receptors must be able to pass through the plasma membrane • Examples of signals that bind to intracellular receptors are: Nitric oxide, steroid and thyroid hormones Pathways Relay Signals From Receptors to Cellular Responses • The signal molecule is not physically passed along the transduction pathway. • The information is passed along. • It is converted or transduced at each step. Protein Phosphorylation • Transfer of a phosphate group • From ATP to a protein substrate (serine or threonine residues) • Catalyzed by protein kinases • Regulates functional activity of proteins • 1% of our genes code for protein kinases • Effects of protein kinases are reversed by protein phosphatases A Phosphorylation Cascade. Cyclic AMP (cAMP) •Some signaling systems rely on small non-protein water soluble molecules or ions. •These are called second messengers. •Examples: cAMP cAMP as a Second Messenger. Amplification Cytoplasmic Response to a Signal. Cellular Responses Signaling can effect the function or activity of proteins that carry out various processes such as: – Rearrangement of the cytoskeleton – Opening or closing of an ion channel – Serve at key points in metabolic pathways – Modulation of gene expression in the nucleus Nuclear Response to a Signal. Signal Specificity • A particular signal can bind to different cell types and result in different responses in each cell • Example, epinephrine action • In liver cells – glycogen breakdown • In cardiac muscle cells – contraction