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 Cell Communication

2.  Cell-to-cell communication is essential for multicellular organisms  Universal mechanisms of cellular regulation  Combined effects of multiple signals determine cell response  Example: dilation of blood vessels is controlled by many molecules Nitric oxide Myosin Signaling molecule called MAP kinase Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

3.  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  Microbes are a window on the role of cell signaling in the evolution of life Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

4. Fig. 11-2 Receptor  factor a factor a   a Exchange of mating factors Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell a/  1 2 3

5.  Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes  Concentration of signaling molecules allows bacteria to detect population density Cluster together Coordination of activities Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

6. Fig. 11-3 Individual rod- shaped cells Spore-forming structure (fruiting body) Aggregation in process Fruiting bodies 0.5 mm 1 3 2

7.  In multicellular organisms, long distance communication is by chemical messengers  Local signaling intercellular connections (plasmodesmata and gap junctions) connect the cytoplasm of adjacent cells communicate by direct contact, or cell-cell recognition Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

9.  In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances  In long-distance signaling, plants and animals use chemicals called hormones Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

11.  Earl W. Sutherland discovered how the hormone epinephrine acts on cells 1971 Nobel Prize  Cells receiving signals went through three processes: Reception (detection of signaling molecule) Transduction (converts signal to relay or form that can bring about cell change) Response (enz. catalysis, cytoskeleton mvmt. gene activation) Animation: Overview of Cell Signaling Animation: Overview of Cell Signaling Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

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

14. 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

15.  Binding between signal molecules (ligands) and receptors = highly specific  Shape change in receptor -- initial transduction of the signal  Most signal receptors are plasma membrane proteins Receptors for testosterone or estrogen are cytoplasmic Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

16.  Water-soluble signal molecules bind to specific receptors in plasma membrane insulin  3 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

17.  Widespread & diverse functions Highly conserved throughout evolution vision & smell  Plasma membrane receptor that requires a G protein acts as an on/off switch: when GDP is bound, the G protein is inactive When GTP is bound, G protein is active Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

18. Fig. 11-7a Signaling-molecule binding site Segment that interacts with G proteins G protein-coupled receptor

19. 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 Hormones & neurotransmitters Bacterial toxins (cholera, pertussis, botulism) interfere w/ G proteins

20.  Plasma membrane receptors that attach phosphates to tyrosines  Cell growth & cell reproduction Example: vascular endothelial growth factor (VEGF) stimulates endothelial cells to undergo cell division and migration to form new blood vessels  Ligand binding triggers multiple signal transduction pathways at once Key difference from G protein coupled receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

21. 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

22.  Acts as a gate when the receptor changes shape upon binding ligand - allows specific ions (Na +, K+, Cl- or Ca 2+ ) through the channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

23. 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 Na+/K+ ATPase Ligand gated ion channels -neurotransmitters in CNS -acetylcholine at the neuromuscular junction

24.  Found in the cytosol or nucleus of target cells  Small or hydrophobic chemical messengers can readily cross the membrane to activate receptors Examples: steroid and thyroid hormones  Activated hormone-receptor complex can act as a transcription factor, turning on specific genes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

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

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

28.  Transduction involves many steps  Signal amplification: a few molecules can produce a large cellular response  Provide many opportunities for coordination and regulation of the cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

29.  Molecules that relay signals are mostly proteins  Like falling dominoes, receptors activate another protein, which activates another, and so on, until the protein producing the cellular response is activated  At each step, the signal is transduced into a different form, usually a shape change in a protein  Carried out via phosphorylation chain reaction Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

30.  Signals transmitted by a cascade of protein phosphorylations (adds negative charge to protein & thus changes its conformation)  Protein kinases - enzymes that transfer phosphates from ATP to protein, in a process called phosphorylation Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

31.  Protein phosphatases - enzymes that remove the phosphates from proteins, a process 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

32. 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

33.  Amplify cell’s response  Different points at which response can be regulated  Specificity of response Different cells express different collections of proteins  e.g. liver cells and neurons

34.  Non-protein, water soluble molecules or ions  Readily spread through cytoplasm  Pathways G protein coupled receptors Receptor tyrosine kinases Two most common Two most common Cyclic AMP (cAMP) Cyclic AMP (cAMP) calcium calcium

35.  Many signaling molecules trigger formation of cAMP  Components of cAMP pathways G proteins & G protein-coupled receptors protein kinases  Activates protein kinase A, which initiates phosphorylation cascade  Further regulation of cell metabolism G-protein systems that inhibit adenylyl cyclase Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

37.  Calcium ions (Ca 2+ ) - second messenger in many pathways  Cells can easily regulate its concentration Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Signal triggers an increase in cytosolic calcium Signal triggers an increase in cytosolic calcium Other components involved: Other components involved: inositol triphosphate (IP 3 ) inositol triphosphate (IP 3 ) diacylglycerol (DAG) diacylglycerol (DAG) as additional second messengers

38. EXTRACELLULAR FLUID Fig. 11-12 ATP Nucleus Mitochondrion Ca 2+ pump Plasma membrane CYTOSOL Ca 2+ pump Endoplasmic reticulum (ER) Ca 2+ pump ATP Key High [Ca 2+ ] Low [Ca 2+ ]

39. 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

40. 1. Describe the nature of a ligand-receptor interaction and how such interactions initiate a signal-transduction system 2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, hormone receptors, and ligand-gated ion channels 1. Provide examples for each 3. List two advantages of a multistep signaling cascade 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

41. 5. Define the term second messenger; and describe the role of these molecules in signaling pathways 1. List two examples 6. Explain why different types of cells may respond differently to the same signal molecule (section 11.4) 1. Provide an example Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings