Cell Communication AP Biology Minzenmayer

Cell Signaling A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Signal transduction pathways convert signals on a cell’s surface into cellular responses AP Biology Minzenmayer

Signaling with Direct Contact Cells in a multicellular organism communicate by chemical messengers Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells In local signaling, animal cells may communicate by direct contact, or cell-cell recognition AP Biology Minzenmayer

Local vs. Long Distance Signaling Animal cells communicate using local regulators messenger molecules that travel only short distances long-distance signaling plants and animals use chemicals called hormones AP Biology Minzenmayer

Local Signaling w/o Direct Contact e.g., interferon release by viral-infected cells Paracrine Signaling Synaptic Signaling AP Biology Minzenmayer

Long-Distance Signaling Hormone Signaling AP Biology Minzenmayer

Long-Distance Diffusion Note how specificity is determined by presence/absence of receptor protein Long-Distance Diffusion AP Biology Minzenmayer

Signal Transduction Plasma membrane 1 Reception Receptor Signaling Fig. 11-6-1 Signal Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception Receptor Signaling molecule

Signal Transduction Plasma membrane 1 Reception 2 Transduction Fig. 11-6-2 Signal Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule

Signal Transduction Plasma membrane Reception Transduction Response Fig. 11-6-3 Signal Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule

Signal Transduction Often turning on or off enzyme activity In this case the receptor protein is a membrane protein Ligand AP Biology Minzenmayer

Wrap-Up How are receptor ligand interactions similar to enzyme substrate interactions? AP Biology

Warm Up In picture A, label the following: -cell -ligand -receptor -membrane channel AP Biology

Warm Up Which diagram depicts communication between cells that are in close proximity? AP Biology

Warm Up Which diagram depicts long distance communication between cells? AP Biology

Warm Up In which type of communication would the ligand need to have the longest “life”? AP Biology

What’s the point of Cell Communication?? Examples: Epinephrine stimulates the breakdown of glycogen in mammals Temperature determines sex of some vertebrate organisms DNA repair mechanisms AP Biology

AP Biology

How does cell communication work? AP Biology

Receptors in Plasma Membrane three main types of membrane receptors: G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors STEP 1: RECEPTION AP Biology Minzenmayer

G Proteins G protein-coupled receptor plasma membrane receptor that works with the help of a G protein G protein acts as an on/off switch: If GDP is bound to the G protein, G protein is inactive AP Biology Minzenmayer

G-Protein-Linked Receptor G proteins bind GTP AP Biology Minzenmayer

G-Protein-Linked Receptor Fig. 11-7b The more ligand binding, the greater the cellular response G protein-coupled receptor Plasma membrane Inactive enzyme Activated receptor Signaling molecule GDP G protein (inactive) Enzyme GDP GTP CYTOPLASM 1 2 Activated enzyme GTP GDP P i Cellular response 3 4

Tyrosine Kinases Receptor tyrosine kinases membrane receptors that attach phosphates to tyrosines can trigger multiple signal transduction pathways at once AP Biology Minzenmayer

Protein Kinase & Phosphatase responses tend to continue (or expand) only so long as signaling continues reversibility contributes to the dynamic nature of cells reversibility of phosphorylation makes signaling reversible AP Biology Minzenmayer

Tyrosine Kinase Receptor Receptor dimerization Ligand Reception Protein Activation Phosphorylization Transduction Response AP Biology Minzenmayer

Ligand Gated Ion Channel ligand-gated ion channel receptor acts as gate when receptor changes shape When signal molecule binds as a ligand to receptor, gate allows specific ions, such as Na+ or Ca2+, through a channel in receptor AP Biology Minzenmayer

Reversibility is assured by pumping ions back out again (using separate protein) Ion-Channel Receptor AP Biology Minzenmayer

Wrap-Up Would a hydrophobic molecule be expected to have an internal or membrane receptor? AP Biology

Modeling Reception Work in groups of 3-4 Choose either G-Protein System or Tyrosine-Kinase Receptor System Build a model Film your group “acting out” model – think of this as a tutorial video for peers Email video to ellen.quigley@springbranchisd.com Best videos will be uploaded to website AP Biology

Modeling Reception Use rest of class period today/finish after school GOAL: model TODAY; film Friday Film due Friday @ end of class Questions due MONDAY 1/12/14 AP Biology

1. What is local signaling? QUIZ 1. What is local signaling? AP Biology

2. What is endocrine signaling? QUIZ 2. What is endocrine signaling? AP Biology

3. What are the three phases of cell signaling? QUIZ 3. What are the three phases of cell signaling? AP Biology

4. How are intracellular receptors different from membrane receptors? QUIZ 4. How are intracellular receptors different from membrane receptors? AP Biology

5. What is the result of signal amplification? QUIZ 5. What is the result of signal amplification? AP Biology

Intracellular Receptors Some receptor proteins are intracellular found in cytosol or nucleus of target cells Examples of messengers steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor turning on specific genes AP Biology Minzenmayer

Intracellular Receptor Fig. 11-8-1 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Intracellular Receptor DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor NUCLEUS CYTOPLASM

Intracellular Receptor Fig. 11-8-2 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex Intracellular Receptor DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor NUCLEUS CYTOPLASM

Intracellular Receptor Fig. 11-8-3 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex Intracellular Receptor DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor NUCLEUS CYTOPLASM

Intracellular Receptor Fig. 11-8-4 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex Intracellular Receptor DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor mRNA NUCLEUS CYTOPLASM

Intracellular Receptor Fig. 11-8-5 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex Intracellular Receptor DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor mRNA NUCLEUS New protein CYTOPLASM

Intracellular Receptor AP Biology Minzenmayer

Transduction molecules that relay a signal from receptor to response are mostly proteins Like falling dominoes, receptor activates another protein, which activates another, …..until protein producing response is activated At each step, signal is transduced into a different form, usually a shape change in a protein AP Biology Minzenmayer

Protein Phosphorylation & Dephosphorylation In many pathways, signal is transmitted by cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Protein phosphatases remove phosphates from proteins, a process called dephosphorylation phosphorylation and dephosphorylation system acts as molecular switch, turning activities on and off AP Biology Minzenmayer

Phosphorylation Cascade Signaling molecule Receptor Activated relay molecule Activates protein kinase Inactive protein kinase 1 Active PK1 transfers P From ATP to inactive PK2 Active protein kinase 1 Inactive protein kinase 2 Phosphorylation cascade ATP Active protein kinase 2 ADP P PP P i Inactive protein kinase 3 ATP ADP Active protein kinase 3 P Protein phosphatases (PP) catalyze removal of P to make them inactive again PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i

Small Molecules & Ions Second Messengers extracellular signal molecule that binds to receptor is a pathway’s “first messenger” Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases Cyclic AMP and calcium ions are common second messengers AP Biology Minzenmayer

Cyclic AMP cAMP Adenylyl cyclase widely used second messengers converts ATP to cAMP in response to extracellular signal AP Biology Minzenmayer

cAMP Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G proteins G protein-coupled receptors protein kinases cAMP usually activates protein kinase A, which phosphorylates various other proteins Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase AP Biology Minzenmayer

cAMP as a 2nd Messenger First messenger Adenylyl cyclase G protein GTP Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP cAMP as a 2nd Messenger ATP Second messenger cAMP cGMP acts as signaling molecule that affects relaxation of smooth muscle cells in artery walls. Compound that inhibits hydrolysis of cGMP to GMP (prolongs signal) was originally prescribed for chest pain…it increased blood flow to heart muscle…now called viagra and used to treat erectile dysrunction in males because it allows increased blood flow to penis Protein kinase A Cellular responses

Cell Signaling - Disease Cholera Caused by Vibrio cholerae in contaminated water Toxin secreted by V. cholerae in small intestine Toxin modifies G protein involved in salt/water secretion Can no longer hydrolyze GTP Always active - stimulates cAMP production Intestinal cells secrete water/ions Severe diarrhea often lethal due to dehydration and salt imbalance

Cell Signaling - Cholera Intestinal Lumen H2O, ions Ext Int GTP GDP H2O, ions Toxin active inactive Net Effect cAMP Intestinal Cell Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

Calcium Ions & Inositol Triphosphate (IP3) Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration AP Biology Minzenmayer

Nuclear & Cytoplasmic Responses signal transduction pathway leads to regulation of one or more cellular activities response may occur in cytoplasm or may involve action in nucleus Many signaling pathways regulate synthesis of proteins usually by turning genes on or off in nucleus final activated molecule may function as transcription factor AP Biology Minzenmayer

Nuclear Response Growth factor Reception Receptor Phosphorylation Fig. 11-14 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Nuclear Response Inactive transcription factor Active transcription factor Response P DNA Gene NUCLEUS mRNA

Fine Tuning Response Multistep pathways have two important benefits: Amplifying signal and therefore the response Contributing to specificity of response Signal Amplification Enzyme cascades amplify cell’s response At each step, number of activated products is much greater than in preceding step Different cells respond differently to same chemical signal ephinephrine triggers striated muscle and liver cells to breakdown glycogen triggers cardiac muscle cells to contract (more rapid heartbeat) Why different responses from same signal? AP Biology Minzenmayer

Signal Amplification (Cascade) AP Biology Minzenmayer

Signal Amplification (Cascade) AP Biology Minzenmayer

WRAP-UP Reception Transduction Response Receptor Activation Fig. 11-UN1 WRAP-UP 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules Signaling molecule