1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Chapter 11 Cell Communication

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview: The Cellular Internet Cell-to-cell comm – essential for multicellular organisms

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Biologists – Have discovered some universal mechanisms of cellular regulation – Viagra blocks enzyme (purple) that shuts down dilation of blood vessels Figure 11.1

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 11.1: External signals are converted into responses w/in the cell

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of Cell Signaling Yeast cells – Identify their mates by cell signaling (a likes to mate w/ α)  factor Receptor Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 1 Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. New a/  cell. The nucleus of the fused cell includes all the genes from the a and a cells. 2 3  factor Yeast cell, mating type a Yeast cell, mating type    a/  a a Figure 11.2

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal transduction pathways – Convert signals on a cell’s surface into cellular responses – similar in microbes & mammals, suggesting an early origin

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local and Long-Distance Signaling Cells in a multicellular organism – Communicate via chem messengers

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Animal & plant cells – Have cell junctions that connect the cytoplasm of adjacent cells Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. In local signaling, animal cells – May communicate via direct contact

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In other cases, animal cells – Comm using local regulators (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. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Target cell is stimulated Local signaling Figure 11.4 A B

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In long-distance signaling – Both plants & animals use hormones (ethylene) 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. Long-distance signaling Blood vessel Target cell Endocrine cell Figure 11.4 C

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Three Stages of Cell Signaling: A Preview Earl W. Sutherland – Discovered how the hormone epinephrine acts on cells

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell signaling, 3 processes; – Reception – Transduction – Response (turn on genes, activate enzymes, etc…)

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Figure 11.5 Overview of cell signaling Reception 1 Transduction 2 Response 3

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings binding b/w signal molecule (ligand) – & receptor is highly specific A conformational change in a receptor – Is often the 1 st transduction of the signal

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Most ligands bind to pm signal receptor proteins b/c they are water-soluble & too big to pass via pm

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Intracellular Receptors Some signal receptors are inside the cell: Intracellular receptors – cytoplasmic or nuclear proteins

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings small or hydrophobic signal molecules – That can readily cross the pm use these receptors

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein DNA mRNA NUCLEUS CYTOPLASM Plasma membrane Hormone- receptor complex New protein Figure 11.6 Steroid hormones – Bind to intracellular receptors 1 The steroid hormone testosterone passes through the plasma membrane. The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5 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

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Receptors in the Plasma Membrane 3 main types of membr receptors – G-protein-linked – Tyrosine kinases – Ion channel

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G-protein-linked receptors G-protein-linked Receptor Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated Receptor Signal molecule Inctivate enzyme Segment that interacts with G proteins GDP GTP P iP i Signal-binding site Figure 11.7 GDP

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings A G-protein-linked receptor is a pm receptor that works w/ the help of a G protein The G-protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Receptor tyrosine kinases Signal molecule Signal-binding sitea 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 Figure 11.7

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Receptor tyrosine kinases are membrane receptors that attach P’s to tyrosines (an aa) A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ion channel receptors Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Figure 11.7 Gate closed Ions

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds to the receptor, the gate allows specific ions; (Na + or Ca 2+ ) through a channel in the receptor

28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Multistep pathways – Can amplify a signal – Provide more opportunities for coordination & regulation

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal Transduction Pathways At each step in a pathway – The signal is transduced into a diff form, (commonly a conformational change in a protein)

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein Phosphorylation and Dephosphorylation Many signal pathways – Include phosphorylation cascades

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Phosphorylation cascade – series of protein kinases add P to the next one in line, activating it – Phosphatase enzymes remove the P’s

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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 ATP ADP ATP PP Activated relay molecule i Phosphorylation cascade P P i i P A phosphorylation cascade Figure 11.8 A relay molecule activates protein kinase 1. 1 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. 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

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Small Molecules and Ions as Second Messengers 2 nd messengers – small, nonprotein, water-soluble molecules or ions

34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1. Cyclic AMP (cAMP) – made from ATP Figure 11.9 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

35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Many G-proteins – Trigger the formation of cAMP, which acts as a 2 nd messenger in cell pathways ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein First messenger (signal molecule such as epinephrine) Figure 11.10

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Calcium ions and Inositol Triphosphate (IP 3 ) 2. Ca, when released into the cytosol of a cell – Acts as a 2 nd messenger in many diff pathways

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ca- impt 2 nd messenger – B/c cells can regulate its concen in the cytosol EXTRACELLULAR FLUID Plasma membrane ATP CYTOSOL ATP Ca 2+ pump Endoplasmic reticulum (ER) Nucleus Mitochondrion Key High [Ca 2+ ]Low [Ca 2+ ] Figure 11.11

38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other second messengers such as inositol triphosphate (IP3) & diacylglycerol (DAC) – Can trigger an increase in calcium in the cytosol

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.12 3 21 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. 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 Various proteins activated Endoplasmic reticulum (ER) Phospholipase C PIP 2 IP 3 (second messenger) DAG Cellular response GTP Ca 2+ (second messenger) Ca 2+ IP 3 -gated calcium channel

40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription (txn)

41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytoplasmic and Nuclear Responses In cytoplasm – Signaling pathways regulate a variety of cellular activities

42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytoplasmic response to a signal Figure 11.13 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

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other pathways – Regulate genes by activating txn factors that turn genes on or off Reception Transduction Response mRNA NUCLEUS Gene P Active transcription factor Inactive transcription factor DNA Phosphorylation cascade CYTOPLASM Receptor Growth factor Figure 11.14

44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Fine-Tuning of the Response Signal pathways w/ multiple steps – amplify signal & add specificity to the response

45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal Amplification Each protein in a signaling pathway – Amplifies the signal by activating multiple copies of the next component in the pathway

46. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Specificity of Cell Signaling The diff combinations of proteins in a cell – Give the cell specificity in both the signals it detects & the responses it carries out

47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Pathway branching & “cross-talk” – Further help the cell coordinate incoming signals Response 1 Response 4Response 5 Response 2 Response 3 Signal molecule 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 Figure 11.15

48. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Scaffolding proteins – Can ↑the signal transduction efficiency Signal molecule Receptor Scaffolding protein Three different protein kinases Plasma membrane Figure 11.16

49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Termination of the Signal Signal response is terminated quickly – By the reversal of ligand binding