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 Cellular Communication References: Chapter 11 Campbell Biology 7 th edition http://library.thinkquest.org/C004535/cellular_signaling.html

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview: The Cellular Internet Cell-to-cell communication is absolutely essential for multicellular organisms – Many living organisms contain billions of cells that carry out diverse functions. – In order for the cells to cooperate, cells need to be able to communicate with each other. – Many of the genes that cells are capable of synthesizing are thought to be involved in cellular signaling (a.k.a. “signal transduction”).

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 11.1: External signals are converted into responses within the cell Biologists have discovered some universal mechanisms of cellular regulation Signal transduction pathways – Convert signals on a cell’s surface into cellular responses – Are similar in microbes and mammals, suggesting an early origin Figure 11.1

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of Cell Signaling Yeast cells – Identify their mates by cell signaling  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

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local and Long-Distance Signaling Cells in a multicellular organism – Communicate via chemical messengers This communication involves ligands - signal triggering molecules, binding to a site on a target protein. Very specific fit required to “dock” with receptor

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chemical Signaling Between Cells Three general categories of chemical signaling: Cytoplasmic connections between cells Cell-to-cell contact-mediated signaling Free diffusion between cells Distant cells (hormones) Adjacent cells (within interstitial space)

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chemical Signaling Between Cells

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Junctions: cytoplasmic connections Animal and plant cells – Have cell junctions that directly 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. Direct Contact In local signaling, animal cells – May communicate via direct contact

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local Signaling Paracrine signaling is a form of cell signaling in which the target cell is near ("para" = near) the signal-releasing cell. Mode of action: Most of these molecules degrade very quickly, limiting the scope of their effectiveness to the immediate surroundings. Paracrine molecules must not be allowed to diffuse too far. Examples: Growth factor and clotting factors are paracrine signaling agents. The local action of growth factor signaling plays an especially important role in the development of tissues.

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local Signaling Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. b. Paracrine Signaling Secretory cell Adjacent target cells

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local Diffusion e.g., Histamine released from damaged cells in inflammation e.g., Interferon release by viral-infected cells

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Neurotransmitters Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.. Synaptic Signaling Nerve cell Neurotransmitter Synaptic gap Target cell neurotransmitters are secreted by neurons to stimulate an adjoining cell For example, a neuron might secrete acetylcholine to stimulate the movement of a muscle cell.

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local Diffusion Note both absence of and lack-of-dependence on Systemic Circulation

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Hormones: long-distance signaling Both plants and animals use hormones 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 Hormones are used for communication with distant target cells. For example, cells can secret a chemical and rely on the blood system to deliver the signal to a distant cell.

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Long-Distance Diffusion Note how specificity is determined by receptor protein Note dependence on Systemic Circulation (blood/lymph)

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal-Transduction Emphasis This chapter’s emphasis is on signals that are released from one cell and allowed to freely diffuse to a second (or more) recipient cell(s) These communications are deliberately initiated, received, and interpreted in order to increase the physiological coordination of the cells in multicellular organisms We will consider in particular those events that follow the reception of chemical signals We will not dwell on the purpose of the signal We also will not dwell on why and how a given cell released a given signal

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CytoplasmExternal environment Membrane receptor Intracellular receptor Plasma membrane Signal transduction pathway Signal transduction pathway Cellular response Cellular response Hydrophobic ligand Hydrophilic ligand

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three Stages of Signal Transduction 1.Reception of extracellular signal by cell 2.Transduction of signal from outside of cell to inside of cell—often multi-stepped Note not necessarily transduction of ligand 3.Cellular Response Response is initiated and/or occurs entirely within receiving cell

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three Stages of Signal Transduction Play with clay

21. 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 The binding between signal molecule (ligand) and receptor is highly specific A conformational change in a receptor is often the initial transduction of the signal

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ligands e.g., steroid hormones e.g., nitric oxide

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three Stages 2a. Transduction 2b. Transduction 2c. Transduction 2d. Transduction 1. Reception 3. Response Responses usually involve increasing or decreasing some Protein’s Function

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three Stages 2a. Transduction 2b. Transduction 1. Reception 3. Response

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Various Responses Note that more than one response can result from the reception of a single ligand

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Various Responses

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Intracellular Receptors Intracellular receptors – Are cytoplasmic or nuclear proteins Signal molecules that are small or hydrophobic – And can readily cross the plasma membrane use these receptors

28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Extracellular Reception e.g., insulin e.g., epinephrine

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Intracellular Reception

30. 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

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Receptors in the Plasma Membrane There are three main types of membrane receptors – G-protein-linked – Tyrosine kinases – Ion channel

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Examples of Surface Receptors

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G Protein-Linked Receptors

34. 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 G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins eukaryotesyeastchoanoflagellatesligandsodors pheromoneshormonesneurotransmitterspeptides proteins

35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G Protein-Linked Receptors note how activation is reversible the more ligand binding, the greater the cellular response

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G Protein-Linked Receptors the more ligand binding, the more K + in cytoplasm

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tyrosine Kinase Receptors Note steps involved: 1.Ligand Reception 2.Receptor Dimerization 3.Catalysis (Phosphorylization) 4.Subsequent Protein Activation 5.Further Transduction 6.Response

38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tyrosine Kinase Receptors

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ion-Channel Receptors

40. 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 and regulation

41. 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

42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal Amplification (Cascade) Note how, via catalysis, one ligand molecule binding gives rise to many new intracellullar molecules

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

44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In this process – A series of protein kinases add a phosphate to the next one in line, activating it – Phosphatase enzymes then remove the phosphates

45. 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

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

47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Second Messengers

48. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other second messengers such as inositol triphosphate and diacylglycerol – Can trigger an increase in calcium in the cytosol

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

50. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Calcium is an important second messenger – Because cells are able to regulate its concentration 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

51. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclic AMP Cyclic AMP (cAMP) – Is 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

52. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Epinephrine  Glycogen Breakdown 10 8 mol Glu-1-Phosphate

53. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Many G-proteins – Trigger the formation of cAMP, which then acts as a second messenger in cellular 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

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

55. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other pathways – Regulate genes by activating transcription 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

56. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Fine-Tuning of the Response Signal pathways with multiple steps – Can amplify the signal and contribute to the specificity of the response

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

58. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Essential knowledge 3.D.4: Changes in signal transduction pathways can alter cellular response. a. Conditions where signal transduction is blocked or defective can be deleterious, preventative or prophylactic. To foster student understanding of this concept, instructors can choose an illustrative example such as: Diabetes, heart disease, neurological disease, autoimmune disease, cancer, cholera Effects of neurotoxins, poisons, pesticides Drugs (Hypertensives, Anesthetics, Antihistamines and Birth Control Drugs) ✘✘ Specific mechanisms of these diseases and action of drugs are beyond the scope of the course and the AP Exam.