1. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp IP16 Cell Communication Page 100 3D1: Cell communication processes share common features that reflect a shared evolutionary history 3D2: Cells communicate with each other though direct contact with other cells or from a distance via chemical signaling. 3D3: Signal transduction pathways link signal reception with cellular response 3D4: Changes in signal transduction pathways can alter cellular response

2. Overview: The Cellular Internet Three main ways cells communicate: – Cell-to-cell (post-it-note) Immune cells using antigen presenting cells Plasmodesmata/Gap Junctions – Short Distances (Email) Local Regulators such as Neurotransmitters – Long distances (facebook) Endocrine cells release hormones through blood to communicate with target cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

3. Fig. 11-4 Plasma membranes Gap junctions between animal cells (a) Cell junctions Plasmodesmata between plant cells (b) Cell-cell recognition

4. Fig. 11-5ab Local signaling Target cell Secretory vesicle Secreting cell Local regulator diffuses through extracellular fluid (a) Paracrine signaling (b) Synaptic signaling Target cell is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter

5. Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

6. Evolution of Cell Signaling Signal Transduction Pathway (STP): a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Biologists have discovered some universal mechanisms of cellular communication shared between yeast and mammals – These pathways similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes

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

8. Evolution of Cell Signaling Continued In single-celled organisms signal transduction pathways influence how the cell responds to its environment: – Quorum sensing: bacteria’s ability to sense the local population size based on the concentration of signaling molecules Can lead to coordination of activities – Biofilms: collections of bacteria that often form recognizable structures that contain regions of specialized functions.

9. Fig. 11-3 Individual rod- shaped cells Spore-forming structure (fruiting body) Aggregation in process Fruiting bodies 0.5 mm 1 3 2 Soil-dwelling bacteria use chemical signal to share information about nutrient availability. When food is scarce, starving cells secrete a molecule that reaches neighboring cells and stimulates them to aggregate. The cells form a structure, called a fruiting body, that produces thick-walled spores capable of surviving until the environment improves.

10. Evolution of Cell Signaling Continued In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organisms as a whole. – Examples: Epinephrine stimulation of glycogen breakdown in mammals Temperature determination of sex in some vertebrate organisms Animal Immune response DNA repair mechanisms

11. Bozeman 036 Evolution of Cell Communication Set page 102 up for Cornell Notes – 036 – 037 – 038 – 039

12. Local and Long-Distance Signaling Local regulators: messages molecules that travel short distance Hormones: chemicals release from glands in the endocrine system that signal long distances Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

13. The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes: – Reception – Transduction – Response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

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

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

17. Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape Ligand: general name used to refer to the substance that binds to a receptor. – The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

18. Receptors in the Plasma Membrane There are three main types of membrane receptors: – G protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

19. A G protein-coupled receptor is a plasma membrane receptor that works with 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

20. Fig. 11-7b G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme 1 2 3 4

21. Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

22. Fig. 11-7c Signaling molecule (ligand) Ligand-binding site  Helix Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLASM Signaling molecule Tyr Dimer Activated relay proteins Tyr P P P P P P Cellular response 1 Cellular response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP Tyr P P P P P P 1 2 3 4

23. A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na + or Ca 2+, through a channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

24. Fig. 11-7d Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1

25. Intracellular Receptors Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

26. Fig. 11-8-1 Hormone (testosterone) Receptor protein Plasma membrane EXTRACELLULAR FLUID DNA NUCLEUS CYTOPLASM

27. Fig. 11-8-2 Receptor protein Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

28. Fig. 11-8-3 Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

29. Fig. 11-8-4 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM

30. Fig. 11-8-5 Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM

31. Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves multiple steps Multistep pathways can amplify a signal: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

32. Signal Transduction Pathways The molecules that relay a signal from receptor to response are mostly proteins Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

33. Signal Transduction Pathway Summary A receptor protein recognizes a signal molecules, causing the receptor protein to change shape which initiates transduction of the signal which ultimately leads to a response from the cell – Movement of the cell membrane – Expression of a gene (transcribed DNA)

34. Protein Phosphorylation and Dephosphorylation Many signal transduction pathways occur as a result of a cascade of protein phosphorylation. Protein kinases: enzyme that transfers phosphates from ATP to protein – This process is called phosphorylation Protein phosphatases: enzyme that removes the phosphates from proteins – This process is called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

35. Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P P PP Inactive protein kinase 3 ATP ADP Active protein kinase 3 P P PP i ATP ADP P Active protein PP P i Inactive protein Cellular response Phosphorylation cascade i

36. Small Molecules and Ions as Second Messengers The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion and act to further carry the message (intermediates) Common second messengers include: – Cyclic AMP and calcium ions Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

37. Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal cAMP usually activates protein kinase A, which phosphorylates various other proteins Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

38. First messenger Fig. 11-11 G protein Adenylyl cyclase GTP ATP cAMP Second messenger Protein kinase A G protein-coupled receptor Cellular responses

39. Calcium Ions and Inositol Triphosphate (IP 3 ) Calcium ions (Ca 2+ ) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration Pathways leading to the release of calcium involve inositol triphosphate (IP 3 ) as additional second messengers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

40. Fig. 11-13-3 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Various proteins activated Cellular responses Ca 2+ (second messenger ) GTP

41. Nuclear and Cytoplasmic Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm or may involve action in the nucleus Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule may function as a transcription factor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

43. Fine-Tuning of the Response Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) – Contributing to the specificity of the response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

44. Signal Amplification Enzyme cascades amplify the cell’s response At each step, the number of activated products is much greater than in the preceding step Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

45. Termination of the Signal Inactivation mechanisms are an essential aspect of cell signaling When signal molecules leave the receptor, the receptor reverts to its inactive state Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

46. Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide A cell is chopped and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by: – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

47. You should now be able to: 1.Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system 2.Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels 3.List two advantages of a multistep pathway in the transduction stage of cell signaling 4.Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell 5.Define the term second messenger; briefly describe the role of these molecules in signaling pathways Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

48. Add more on the endocrine System