BIOL 3510 Lecture 16 Cell Signaling I PDF

BIOL 3510: Lecture 16 Cell signaling I (Ch. 16) General principles of cell signaling Objectives: ▪ Recognize general principles of cell signaling. ▪ Compare and contrast endocrine, paracrine, neuronal, and contact-dependent signaling. This includes general mode of action and example signa...

BIOL 3510: Lecture 16 Cell signaling I (Ch. 16) General principles of cell signaling Objectives: ▪ Recognize general principles of cell signaling. ▪ Compare and contrast endocrine, paracrine, neuronal, and contact-dependent signaling. This includes general mode of action and example signaling molecules. Interpret downstream actions and sample signaling pathways based on their general principles. ▪ List molecular factors that determine the response of a cell to a signal. Explain and apply the following terms: primary transduction, relay, transduce, amplify, integrate, distribute, scaffold, small intracellular messenger molecules, protein phosphorylation, kinase, phosphatase, extracellular signal molecules, receptor protein, effector proteins, target cell responses, signaling cascade. ▪ Compare and contrast three classes of cell-surface receptors focusing on general structural elements and mechanisms.  General principles of cell signaling coxtaperonse Signal transduction is the process whereby one type of signal is converted into another.  General principles of cell signaling ▪ Signals can act over a long or short range. ▪ A limited set of extracellular signals can produce a huge variety of cell behaviors. ▪ A cell’s response to a signal can be fast or slow. ▪ Cell-surface receptors relay extracellular signals via intracellular signaling pathways. ▪ Some intracellular signaling proteins act as molecular switches. ▪ Cell-surface receptors fall into three main classes. ▪ Ion-channel-coupled receptors convert chemical signals into electrical ones.  Types of cell signaling – 1. Endocrine Hormone Molecules ▪ Signal molecules (hormones) are secreted by endocrine cells into the bloodstream (animals) or sap (plants). ▪ Long-range signaling ▪ Systemic impact Examples: Estrogen (ovary), Testosterone (testes), Insulin (pancreas) Examples of endocrine signal molecules Epinephrine a Estradiol Cortisol Thyroxine (T4 Hormone) Types of cell signaling – 2. Paracrine ▪ Signal molecules diffuse in the extracellular fluid and act as local mediators to target cell (neighborhood). ▪ Usually elicits quick responses that last only a short period of time ▪ Ligand molecules are normally quickly degraded by enzymes or removed by neighboring cells Gayest plong slow Q: how does paracrine signaling differ from endocrine signaling? speed  g Types of cell signaling – 2. Paracrine EGF 6-kDa (53 amino acid residues ) Types of cell signaling – 2. Paracrine ▪ Signal molecules diffuse in the extracellular fluid and act as local mediators to target cell (neighborhood). ▪ If the secreting cell responds, autocrine signaling (or self-signaling). essential in various physiological processes (growth regulation, immune responses, and cellular differentiation) e.g., cytokine interleukin-1 in monocytes Types of cell signaling – 3. Neuronal ▪ Signal molecules (neurotransmitters) are delivered to a specific target cell at the synapse. ▪ Highly specific and fast Q: what are the major similarities and differences between neuronal and paracrine signaling? FLETTEN TIME andprecise host cells Paracrine Types of cell signaling – 4. Contact-Dependent ▪ The signaling and target cells are in direct physical contact. ▪ The signal molecule is NOT released by the signaling cell – surface-bound and interacts with receptor on target cell ▪ Also includes signaling through gap junctions between adjacent cells iClicker Question Which of the following signaling types involves hormones being released into the bloodstream to affect distant target cells throughout the body? A. paracrine. B. endocrine. C. contact-dependent. D. neuronal.  Response of a cell to a signal What determines the response of a cell to a signal? pest ▪ Presence or absence of the receptor. ▪ Presence or absence of intracellular signaling proteins and intracellular effector proteins: - change in gene expression, metabolism, movement, shape, status ▪ Combinations of signals give different responses.  Response of a cell to a signal Extracellular signaling molecules can bind cell-surface receptors or intracellular receptors: Q: steroid hormones act on which type of receptors? why? A  Response of a cell to a signal The same signal molecule can induce different responses in different target cells. E.g. Different cell types respond to acetylcholine differently. M2 muscarinic M3 muscarinic N1 nicotinic  Response of a cell to a signal Combination of signals produce different effects. E.g. An animal cell depends on multiple extracellular signals.  Response of a cell to a signal Timing in cell’s response can be: ▪ Fast: change in protein activity. ▪ Slow: change in gene expression, cell growth and division. Response of a cell to a signal ▪ Many extracellular signals activate intracellular signal pathways to change the behavior of the target cell. ▪ Binding of a signal molecule to a cell surface receptor produces a variety of responses.  Response of a cell to a signal - Example cortisol Some hormones cross the plasma membrane and bind intracellularly: ▪ Steroid and thyroid hormones bind nuclear receptors intracellularly promoting transcription. ▪ Steroid hormones = cortisol, estradiol, testosterone ▪ Thyroid hormone = thyroxine Response of a cell to a signal - Example NO depending has slow or fast fast Steroids expression No gene ▪ Some gases cross the plasma on getup membrane and bind expression intracellularly. Gene hours Minutes ▪ Release of nitric oxide (NO) from endothelial cells promotes relaxation of smooth muscle. Q: is this a fast or slow response? Fast response has many steps eventhough  Response of a cell to a signal Intracellular signaling molecules: ▪ can relay, amplify, integrate and distribute an incoming signal. ▪ form a signaling cascade. ▪ engage in feedback.  Feedback regulation Enhances stability ▪ Enhances the initial signal by ▪ Reduces or inhibits the activity of increasing the activity of an earlier an earlier component within the component within the pathway. pathway. ▪ Leads to a rapid and sustained ▪ Prevents overactivation and response. maintain balance. ▪ In some signaling pathways, the ▪ This is often the primary product of the pathway activates its mechanism to prevent excessive own production or the production of signaling and restore equilibrium. additional signaling molecules.  iClicker Question Some signaling molecules can activate more than one receptor leading to differing outcomes in different cell types depending on the receptors present in each cell. Acetylcholine can activate muscarinic G-protein-coupled receptors and nicotinic receptor ion channels. Some snakes like cobras and mambas produce venom that functions as an antagonist of nicotinic receptor ion channels. Which of the following biological effects would you predict to occur after a cobra or mamba snake bite? Choose one: A. Heart rate increases B. Saliva secretion decreases C. Skeletal muscle contraction decreases D. All of these occur.  Response of a cell to a signal Many intracellular signaling proteins behave as molecular switches: receipt of a signal causes them to toggle from an inactivate to an active state. Love phosphate phospho quartet Note: phosphorylation can either activate or inhibit proteins! Response of a cell to a signal The activity of monomeric GTPases is controlled by two types of regulatory proteins: ▪ GEF: Guanine nucleotide exchange factor ▪ GAP: GTPase-activating protein turfffproteinis an eventhough it activationProtein  Three classes of cell-surface receptors 1. Ion-channel-coupled receptor ▪ opens in response to binding an extracellular signal molecule. ▪ is also called transmitter-gated ion channel. A True or False: ion-channel-coupled receptors convert chemical signals into electrical signals. True  Three classes of cell-surface receptors 2. G protein-coupled receptor ▪ Signal molecule binding to a G protein-coupled receptor activates a G-protein. ▪ Then G-protein turns on or off channels or enzymes.  Three classes of cell-surface receptors 3. Enzyme-coupled receptor After molecule signal binding, these receptors act as enzymes or activate enzymes in the cytosolic side.  Response of a cell to a signal Some foreign substances act on cell-surface receptors: iClicker Question Which of the following statements about molecular switches is FALSE? A. Protein kinases transfer the terminal phosphate from ATP onto a protein. B. A GTP-binding protein exchanges its bound GDP for GTP to become activated. C. Phosphatases remove the phosphate from GTP on GTP-binding proteins, turning them off. D. The activity of monomeric GTPases is controlled by GAP and GEF.