Cell Signaling Notes PDF

★ Cell signaling is the series of steps that allow cells to respond to signals from their environment. ★ Cell will respond by initiating some sort of cellular activity....

★ Cell signaling is the series of steps that allow cells to respond to signals from their environment. ★ Cell will respond by initiating some sort of cellular activity. ○ E.g. Initiation of Cell Cycle ★ Signaling usually requires the secretion of ligand (a chemical signal) from the initiating cell that travels to the target cell. ★ Only cells that have the correct What is Cell Signaling? receptor protein will react to the signal molecule.  Basics of Cell Signaling Step 1: Reception Step 2: Transduction Step 3: Response ★ Ligand binds to the ★ Signal is moved ★ The final molecule in receptor. from the cell the signal pathway ★Receptor undergoes a membrane to the activates target DNA conformational nucleus through Gene in the nucleus. (shape) change phosphorylation of a ★ This leads to a ★The shape change series of proteins. protein being made transmits signal inside ★ Phosphorylation = which = cell of the cell adding a phosphate response.  Bell work Answer in your graphic organizer: A scientist is experimenting on mice to see how “Medicine X” affects their rate of insulin production(insulin is a protein made in the liver). Group A received 10 mg/day and group B received 50 mg/day of Medicine X. Further studies showed that medicine X binds to the liver cells and increases the rate of insulin production. Identify the ligand in this experiment, Explain why medicine X would only bind to liver cells. Cells make physical Ligands can travel short contact to transmit Cell to Cell distances through diffusion signals and initiate cell Contact or long distances through the bloodstream. response. 2 Mechanisms of Ligand Delivery Requires direct contact Communicating cell between signal and receptor proteins bound Paracrine releases a signaling molecule (ligand) that on the cell membrane of Signaling moves to the target communicating cells. (receiving cell). Hydrophilic ligands bind to a This complex travels receptor that is embedded in the the cell membrane. The Membrane Bound directly to the nucleus to ligand DOES NOT cross the Receptors initiate cell response, bypassing transduction. membrane. Membrane Bound vs Intracellular Receptors Signal is amplified and Lipid soluble ligands moved from the membrane Intracellular diffuse across the membrane and bind to the to the nucleus via a transduction pathway. Receptors receptor INSIDE of the cell.  Signal Transduction Basics ★ Membrane bound receptors require use of transduction to move the signal from the membrane to the nucleus. ★ Ligand binds to the receptor, causing it to change shape. This transmits the signal into the cell. ★ A second messenger (such as cyclic AMP) is activated and phosphorylates the next protein in the chain to activate it. ★ This occurs over and over until the last protein in the pathway (usually a transcription factor) enters the nucleus and initiates the cell response.  ★ Transduction pathways initiate transcription of target genes. (Genes turn on and make a protein) ★ This ultimately results proteins being made that How do Cells Respond to cause the cell to respond Signal Transduction? appropriately to the signal.  ★ Examples of cell responses include (but are not limited to): ○ Causing the cell to grow and enter the cell cycle. ○ Stimulating cells to secrete molecules How do Cells Respond to ○ Initiation of cell death (apoptosis) Signal Transduction?  G Protein Coupled Receptors (GPCRs) a signaling example ★ Ligand binds to the GPCR, ★ Phosphorylated G protein causing it to phosphorylate activates the second and activate the G Protein messenger, initiating transduction and leading to the cell response.  Bell work Answer in your graphic organizer: A mutation in a section of DNA that codes for the receptor protein of insulin changes the shape of the receptor protein. When insulin is detected by a cell it increases the amount of glucose used by the cell. Predict how this mutation would affect the usage rate of glucose in target cells. Besides mutations, what else might decrease a cell’s response to a ligand?  ★ Mutations that lead to a change in shape and chemical affinity in signaling molecules, receptor molecules, or any of the proteins involved in transduction can change or Structure, Function, and stop the cell response from occurring properly. Pathway Malfunction  ★ Many medicines and toxins work by activating or inhibiting signaling pathways. ★ Example: Botulinum Toxin (Botox) ○ Botox molecules break down SNARE protein, which is required for release of neurotransmitters. ○ Neurotransmitters are not Chemical Compounds and released, causing paralysis of the muscles. Pathway Interference  Feedback Mechanisms ★ Sensory pathways and responses that your body uses to maintain homeostasis. ★ Two types Negative Feedback Slows down or stops a response. Positive Feedback Amplifies or increases a response.  Positive feedback is Regulate physiological Negative Feedback usually used to produce processes by stopping a cellular response. Mechanisms large systemic changes to reestablish homeostasis. Negative vs. Positive Feedback Mechanisms Stopping the response Responsible for initiating causes the body system to return to its normal state, Positive Feedback and amplifying biological thus re-establishing Mechanisms processes in the body system. homeostasis.  Negative Feedback Practice ★ What would happen to the concentrations of the different intermediates if enzyme 3 were inhibited? ○ Substrate B would build up in the cell because it couldn’t be converted intermediate C. ★ What about if you inhibit Enzyme 5? ○ Substrate D would build up in the cell because it couldn’t be converted into isoleucine.  Bell Work Answer in “Cell Cycle Graphic Organizer”: Why do you think it is so important for organisms to make more cells? Answer at the bottom of the G.O. Pair- Share your answer with your shoulder partner Share- Nishi will call on someone to share their answer.  Most cells in an organism are in the G-0 phase. IMPORTANT PREREQUISITE KNOWLEDGE ALERT This is a fancy way of saying the cells are quiescent* *Which is a fancier way of saying the cells are not going through the cell cycle Series of events in which An organism's cells grow and divide to form two genetically identical diploid daughter* cells *Daughter cells just refer to the two newly produced cells.  ★ Cells going through the cell cycle alternate between two major phases: ➔ Interphase ◆ MAKE ALL THE THINGS and prepare to divide. Cell Cycle Overview ◆ Has 3 subparts ➔ Mitosis (M phase) and This is not all the steps of the cell Cytokinesis cycle ◆ Actual cell division More on this later  Cell Cycle Timing Not all cells divide at the same rate G0 (non-dividing cells) can enter and leave the cell cycle based on environmental signals and cues How long does the cell cycle take? ➔ How often cells divide is usually a function of how often they are “used” or exposed to damaging conditions. ➔ Some cells don’t go through the cell cycle at ➔ Total time: ~24hrs all. ➔ Interphase: 23/ 24 hrs ➔ Mitosis (M Phase): 1/ 24 hrs Developing organisms Asexually reproducing require production of new Developing organisms use the cell cells that each possess a complete genome in order Organisms cycle to pass their DNA to grow. to the next generation. Why do cells go through the cell cycle? Organismal Growth Adult, multicellular organisms occurs when cell Adult utilize the cell cycle in order to replace damaged or dying production is greater Organisms somatic (body) cells (aka tissue than cell death. repair).  Steps of the Cell Cycle 3 Stages: Interphase, Mitosis (M Phase), & Cytokinesis ➔ Interphase ◆ Growth 1 (G1) ◆ Synthesis of DNA (S phase ) ◆ Growth 2 (G2) ➔ Mitosis (M Phase) ◆ Prophase ◆ Metaphase ◆ Anaphase ◆ Telophase ➔ Cytokinesis Steps of the Cell Cycle Stage 1: Interphase Interphase Checklist ➔ Step 1: Growth 1 (G1) ◆ Grow ◆ Produce more VIP molecules* and structures *E.g. nucleotides, enzymes, etc. ➔ DNA Synthesis (S) ◆ DNA REPLICATION ONLY ➔ Growth 2 (G2) ◆ Finish growing ◆ Produce more VIP molecules and structures in preparation for division  Steps of the Cell Cycle 3 Stages: Interphase, Mitosis (M Phase), & Cytokinesis ➔ Interphase ◆ Growth 1 (G1) ◆ Synthesis of DNA (S phase ) ◆ Growth 2 (G2) ➔ Mitosis (M Phase) ◆ Prophase ◆ Metaphase ◆ Anaphase ◆ Telophase ➔ Cytokinesis Prophase Metaphase Anaphase ➔ Nucleus dissolves ➔ Spindle fibers attach to ➔ Contract spindle fibers to chromosomes ➔ DNA condenses, move one set of ➔ Chromosomes line up on the chromosomes are visible chromosomes to opposite equatorial plate (AKA middle ➔ Spindle Fibers Form of the cell) poles of the cell. Mitosis Telophase Cytokinesis (tech not mitosis) ➔ Nucleus Reforms ◆ Cytoplasm divides ➔ DNA Decondenses, reallows DNA ◆ Cell membrane pinches in access ➔ Cell membrane starts pinching in. Checklist to form 2 genetically identical daughter cells.  Mitosis IRL Frog zygote going through the cell cycle to grow and develop during gestation Cells in G0 phase Blue Stain: DNA Red Stain: Mitochondria Somatic cell going through mitosis Green: Microtubules, Green Stain: Microtubules Red: DNA  How do cells know to move to the next step? Differential coexpression of Cyclins and Cyclin Dependent Kinases (CDKs) proteins control cell progression through the cell cycle Excuse me, what? ➔ Growth factor signals the cell to produce checkpoint-specific cyclin proteins. ➔ Cyclin proteins produced via protein synthesis build up in the cell. ➔ At high enough concentrations, cyclin binds to its specific Cyclin Dependent Kinase (CDK). ➔ CDK initiates a phosphorylation cascade that allows the cell pass the checkpoint and continue the cell cycle ➔ Phase specific cyclin is broken down to prevent improper signaling. Each type of cyclin increases to initiate its phase  ★ Cells are required to pass through 3 Cell Cycle Control checkpoints as they progress through the cell cycle. Overview ★ Cells check for damage, mutations and proper internal conditions at each checkpoint. ★ Healthy cells complete the cell cycle :) ★ Damaged/mutated cells enter cell cycle arrest. ○ Cell produces inhibitors of cyclin proteins to prevent progression through the cell cycle. The damaged DNA is repaired and continues through the cell Repairable cycle, eventually producing 2 Damage/Mutation genetically identical daughter cells. What should happen When damage is detected? The cell goes through programmed cell death and is eliminated. No daughter cells Cells must pass all three Irreparable are produced. Diseases like checkpoints in order to complete the cell cycle damage/mutation cancer are prevented. Cancer: A Disease of the Cell Cycle ★ Cancer is uncontrolled cell growth leading to tumors. ★ Cancer cells have an accumulation of mutations in genes that prevent damaged cells from continuing through the cell cycle. ★ These mutations prevent programmed cell death and allow the cancer cell to grow and divide unlimitedly.  One or more Checkpoints failed Apoptosis: Programed cell death, initiated by itself Checkpoint failed to catch the mistake 2 mistaked must occur: 1. Mistake in gene that codes for replication 2. Mistake in gene that codes for apoptosis or checkpoints