1. Please turn in your completed case study (all parts!)

2. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? -Paracrine – local signaling from 1 cell to another in close range -Endocrine – long-distance signaling involving hormones (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Local regulator diffuses through extracellular fluid Secreting cell Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Target cell is stimulated Local signalingLong-distance signaling Endocrine cell Blood vessel Target cell

3. Figure 11.3 Communication by direct contact between cells Plasma membranes (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. Plasmodesmata between plant cells Gap junctions between animal cells

4. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor EXTRACELLULAR FLUID Receptor Signal molecule Plasma membrane CYTOPLASM ReceptionTransduction 12

5. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor -Transduction – conversion of the received signal to a specific cellular response EXTRACELLULAR FLUID Receptor Signal molecule Plasma membrane CYTOPLASM ReceptionTransduction 12 Relay molecules in a signal transduction pathway

6. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor -Transduction – conversion of the received signal to a specific cellular response -Response – cell’s response to the signal EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response ReceptionTransductionResponse 123

7. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? 3.What are the 4 types of receptors? -Intracellular receptors…..aka steroid hormone receptors -G-protein-linked receptors -Tyrosine kinase receptors -Ligand-gated ion channels -membrane-bound (integral proteins)

8. Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM New protein The non-polar steroid hormone testosterone passes through the plasma membrane. 1 Testosterone binds to a receptor protein in the cytoplasm, activating it. 2 The hormone- receptor complex enters the nucleus and binds to specific genes. 3 The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5 Fig. 11.6 Steroid hormone interacting with an intracellular receptor

10. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? 3.What are the 4 types of receptors? -Intracellular receptors…..aka steroid hormone receptors -G-protein-linked receptors -Associated with a cytoplasmic G-protein -G-protein binds either GDP (inactive) or GTP (active) -Ligand binding -Causes a change in receptor shape which -Attracts the inactive G-protein -GTP displaces GDP activating the G-protein -Activated G-protein can then activate other specific molecules

11. Figure 11.7 Exploring Membrane Receptors Signal-binding site G-PROTEIN-LINKED RECEPTORS G-protein-linked receptor Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated receptor Signal molecule Inactive enzyme Segment that interacts with G proteins GDP GTP P iP i GDP

12. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? 3.What are the 4 types of receptors? -Intracellular receptors…..aka steroid hormone receptors -G-protein-linked receptors -Tyrosine kinase receptors -Kinase – enzyme that phosphorylates -Ligand binding -Causes receptor to form a dimer -Cytoplasmic tails phosphorylate each other because… -ATP is hydrolyzed & terminal phosphate is added to tyrosine aa -Activated receptors can then activate specific relay proteins

13. RECEPTOR TYROSINE KINASES Signal molecule Signal-binding site CYTOPLASM Tyrosines Signal molecule  Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P P P P P P Tyr P P P P P P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) 6 ATP 6 ADP

14. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? 3.What are the 4 types of receptors? -Intracellular receptors…..aka steroid hormone receptors -G-protein-linked receptors -Tyrosine kinase receptors -Ligand-gated ion channels -Ligand binding -Causes a change in shape -Allows specific ions to move down concentration gradient -e.g. neurotransmitters between neurons

15. Gate close Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Gate Closed Ions ION CHANNEL RECEPTORS

16. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor -Transduction – conversion of the received signal to a specific cellular response EXTRACELLULAR FLUID Receptor Signal molecule Plasma membrane CYTOPLASM ReceptionTransduction 12 Relay molecules in a signal transduction pathway

17. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor -Transduction – conversion of the received signal to a specific cellular response -Often done by protein phosphorylations -Protein kinases phosphorylate other relay molecules (kinases) -Inactivated by phosphatases

18. Figure 11.8 A phosphorylation cascade (involves several protein kinases) Signal molecule Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 1 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein Cellular response Receptor P P P P P P ATP ADP ATP PP Activated relay molecule A relay molecule activates protein kinase 1. 1 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. 2 Active protein kinase 2 then catalyzes the phos- phorylation (and activation) of protein kinase 3. 3 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 4 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 5 i i i Phosphorylation cascade

19. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor -Transduction – conversion of the received signal to a specific cellular response -Often done by protein phosphorylations -2 nd messengers -cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP O –O–OO O N O O O OO P P P P PP O OO O O O OH CH 2 NH 2 N N N N N N N N N N N O O OO ATP Ch 2 CH 2 O OH P OO OO H2OH2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMPAMP OH O i

20. Fig 11.10 cAMP as a second messenger in a G-protein-signaling pathway First messenger (signal molecule such as epinephrine) ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein Second messenger

21. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor -Transduction – conversion of the received signal to a specific cellular response -Often done by protein phosphorylations -2 nd messengers -cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP -Ca +2 ions -Released from ER

22. Figure 11.11 Maintenance of calcium ion concentrations in an animal cell EXTRACELLULAR FLUID Plasma membrane ATP CYTOSOL ATP Ca 2+ pump Endoplasmic reticulum (ER) Nucleus Mitochondrion Key High [ Ca 2+ ]Low [ Ca 2+ ]

23. Figure 11.12 Calcium and IP 3 in signaling pathways IP 3 quickly diffuses through the cytosol and binds to an IP 3 – gated calcium channel in the ER membrane, causing it to open. 4 IP 3 (second messenger) DAG 3 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Endoplasmic reticulum (ER) Phospholipase C PIP 2 GTP Ca 2+ IP 3 -gated calcium channel A signal molecule binds to a receptor, leading to activation of phospholipase C. 12 CYTOSOL How does Ca +2 get released from the ER? - more 2 nd messengers - IP 3 - follow the numbers

24. Figure 11.12 Calcium and IP 3 in signaling pathways Calcium ions flow out of the ER (down their con- centration gradient), raising the Ca 2+ level in the cytosol. 5 321 IP 3 quickly diffuses through the cytosol and binds to an IP 3 – gated calcium channel in the ER membrane, causing it to open. 4 Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Endoplasmic reticulum (ER) Phospholipase C PIP 2 IP 3 (second messenger) DAG GTP Ca 2+ (second messenger) Ca 2+ IP 3 -gated calcium channel DAG functions as a second messenger In other pathways. CYTOSOL

25. Figure 11.12 Calcium and IP 3 in signaling pathways 2 3 IP 3 quickly diffuses through the cytosol and binds to an IP 3 – gated calcium channel in the ER membrane, causing it to open. 4 The calcium ions activate the next protein in one or more signaling pathways. 6 Calcium ions flow out of the ER (down their con- centration gradient), raising the Ca 2+ level in the cytosol. 5 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Various proteins activated Endoplasmic reticulum (ER) Phospholipase C PIP 2 IP 3 (second messenger) DAG Cellular responses GTP Ca 2+ (second messenger) Ca 2+ IP 3 -gated calcium channel A signal molecule binds to a receptor, leading to activation of phospholipase C. 1 CYTOSOL

26. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? -Reception – ligand (signal molecule) binding to a receptor -Transduction – conversion of the received signal to a specific cellular response -Often done by protein phosphorylations -Protein kinases phosphorylate other relay molecules (kinases) -Inactivated by phosphatases -2 nd messengers -cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP -Ca +2 ions -IP 3 - inositol triphosphate -Response – cell’s response to the signal 3.What is meant by signal amplification? -A single ligand can activate millions of molecules during a cell’s response

27. Figure 11.13 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Glucose-1-phosphate (10 8 molecules) Glycogen Active glycogen phosphorylase (10 6 ) Inactive glycogen phosphorylase Active phosphorylase kinase (10 5 ) Inactive phosphorylase kinase Inactive protein kinase A Active protein kinase A (10 4 ) ATP Cyclic AMP (10 4 ) Active adenylyl cyclase (10 2 ) Inactive adenylyl cyclase Inactive G protein Active G protein (10 2 molecules) Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Response Reception - Cytoplasmic signal amplification

28. Figure 11.14 Nuclear responses to a signal: the activation of a specific gene by a growth factor Growth factor Reception Transduction Response mRNA NUCLEUS Gene P Active transcription factor Inactive transcription factor DNA Phosphorylation cascade CYTOPLASM Receptor - Nuclear signal amplification

29. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? 3.What is meant my signal amplification? 4.How can cells have different responses to the same signal? -Different relay proteins -Cross-talk w/ diff. signals -Different receptor types Response 1 Response 4Response 5 Response 2Response 3 Cell A. Pathway leads to a single response Cell B. Pathway branches, leading to two responses Cell C. Cross-talk occurs between two pathways Cell D. Different receptor leads to a different response Activation or inhibition Receptor Relay molecules Signal molecule

30. Chapter 11: Cell Communication 1.What is the difference between paracrine signaling & endocrine signaling? 2.What are the 3 stages of cell signaling? 3.What is meant my signal amplification? 4.How can cells have different responses to the same signal? 5.How do scaffolding proteins help cell communication? - By binding several different molecules together for quicker process Signal molecule Receptor Scaffolding protein Three different protein kinases Plasma membrane