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 How does the structure of a cell allow for cell to cell communication? How does an external signal produce an internal cellular response? Students will understand the function of: G protein receptors Tyrosine kinase receptors Ion gated receptors

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

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Common ancestor – Some mechanisms of cellular regulation are universal: very early origin Figure 11.1

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings External to Internal External signals are converted into responses within the cell – Reception – Transduction – Response

6. 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

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Apocrine Communication: direct contact 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.

8. 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: EMC

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Paracrine: short distance communication In other cases, animal cells – Communicate 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

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Endocrine: long distance communication Cells in a multicellular organism – Communicate via chemical messengers Hormones

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In 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 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 – Epinephrine into test tube with all the chemicals in cell (but cells destroyed) Not functional

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sutherland suggested that cells receiving signals went through three processes – Reception: requires intact cell membrane receptors – Transduction: requires intact transduction pathways – Response

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 Reception Reception: A signal molecule binds to a receptor protein, causing it to change shape Specificity: ligand to target cell

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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

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

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G protein receptors 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

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tyrosine Kinase Receptor: move phosphate groups 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

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ion channel receptors Ion channel receptors: – Allow – Or Hinder the flow of ions Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Figure 11.7 Gate closed Ions

21. 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 Steroids 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

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

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Transduction: Cascades of interactions relay signals from receptors to target molecules in the cell Multistep pathways – Can amplify a signal – coordination and regulation of signals

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

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

26. 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

27. 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 – Ca calcium (muscle contraction) – cAMP (often with G protein)

28. 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

29. 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

30. 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

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Muscle Contraction 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

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Response Response: Cell signaling leads to regulation of – cytoplasmic activities or – Transcription (DNA to RNA)

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Response in Cytoplasm 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

34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Response in Nucleus Transcription factors 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

35. 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 Each protein in a signaling pathway – Amplifies the signal by activating multiple copies of the next component in the pathway

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

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Pathway branching and “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

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

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