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Cell Communication AP Biology Minzenmayer
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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
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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
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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
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Local Signaling w/o Direct Contact
e.g., interferon release by viral-infected cells Paracrine Signaling Synaptic Signaling AP Biology Minzenmayer
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Long-Distance Signaling
Hormone Signaling AP Biology Minzenmayer
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Long-Distance Diffusion
Note how specificity is determined by presence/absence of receptor protein Long-Distance Diffusion AP Biology Minzenmayer
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Signal Transduction Plasma membrane 1 Reception Receptor Signaling
Fig Signal Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception Receptor Signaling molecule
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Signal Transduction Plasma membrane 1 Reception 2 Transduction
Fig Signal Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule
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Signal Transduction Plasma membrane Reception Transduction Response
Fig 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
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Signal Transduction Often turning on or off enzyme activity
In this case the receptor protein is a membrane protein Ligand AP Biology Minzenmayer
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Wrap-Up How are receptor ligand interactions similar to enzyme substrate interactions? AP Biology
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Warm Up In picture A, label the following: -cell -ligand -receptor
-membrane channel AP Biology
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Warm Up Which diagram depicts communication between cells that are in close proximity? AP Biology
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Warm Up Which diagram depicts long distance communication between cells? AP Biology
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Warm Up In which type of communication would the ligand need to have the longest “life”? AP Biology
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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
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AP Biology
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How does cell communication work?
AP Biology
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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
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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
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G-Protein-Linked Receptor
G proteins bind GTP AP Biology Minzenmayer
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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
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Tyrosine Kinases Receptor tyrosine kinases
membrane receptors that attach phosphates to tyrosines can trigger multiple signal transduction pathways at once AP Biology Minzenmayer
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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
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Tyrosine Kinase Receptor
Receptor dimerization Ligand Reception Protein Activation Phosphorylization Transduction Response AP Biology Minzenmayer
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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
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Reversibility is assured by pumping ions back out again (using separate protein)
Ion-Channel Receptor AP Biology Minzenmayer
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Wrap-Up Would a hydrophobic molecule be expected to have an internal or membrane receptor? AP Biology
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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 video to Best videos will be uploaded to website AP Biology
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Modeling Reception Use rest of class period today/finish after school
GOAL: model TODAY; film Friday Film due end of class Questions due MONDAY 1/12/14 AP Biology
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1. What is local signaling?
QUIZ 1. What is local signaling? AP Biology
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2. What is endocrine signaling?
QUIZ 2. What is endocrine signaling? AP Biology
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3. What are the three phases of cell signaling?
QUIZ 3. What are the three phases of cell signaling? AP Biology
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4. How are intracellular receptors different from membrane receptors?
QUIZ 4. How are intracellular receptors different from membrane receptors? AP Biology
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5. What is the result of signal amplification?
QUIZ 5. What is the result of signal amplification? AP Biology
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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
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Intracellular Receptor
Fig Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Intracellular Receptor DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor NUCLEUS CYTOPLASM
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Intracellular Receptor
Fig 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
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Intracellular Receptor
Fig 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
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Intracellular Receptor
Fig 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
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Intracellular Receptor
Fig 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
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Intracellular Receptor
AP Biology Minzenmayer
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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
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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
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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
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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
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Cyclic AMP cAMP Adenylyl cyclase widely used second messengers
converts ATP to cAMP in response to extracellular signal AP Biology Minzenmayer
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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
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cAMP as a 2nd Messenger First messenger Adenylyl cyclase G protein GTP
Fig 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
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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
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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
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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
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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
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Nuclear Response Growth factor Reception Receptor Phosphorylation
Fig Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Nuclear Response Inactive transcription factor Active transcription factor Response P DNA Gene NUCLEUS mRNA
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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
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Signal Amplification (Cascade)
AP Biology Minzenmayer
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Signal Amplification (Cascade)
AP Biology Minzenmayer
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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
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