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 communication – Is absolutely essential for multicellular organisms

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

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of Cell Signaling Yeast cells – Identify their mates by cell signaling Cells in a multicellular organism – Communicate via chemical messengers Animal and plant cells – Have cell junctions that directly connect the cytoplasm of adjacent cells In local signaling, animal cells – direct contact or local regulators

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In long-distance signaling – Both plants and animals use hormones

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sutherland suggested that cells receiving signals went through three processes – Reception – Transduction – Response

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

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Intracellular Receptors Intracellular receptors – Are cytoplasmic or nuclear proteins

9. 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

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

11. 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

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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

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

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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Termination of the Signal Signal response is terminated quickly – By the reversal of ligand binding http://bcs.whfreeman.com/thelifewire/content/chp 15/15020.html