1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell Communication

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Functions of the Cell Membrane So far we focused on how the cell membrane controls what enters and exits the cell The cell membrane also provides a means by which a cell can communicate and interact with other cells and the environment

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How does the cell membrane do this? – External signals are received by proteins or carbohydrates at the cell membrane and converted into responses within the cell – This is called a signal transduction pathway 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 Simplest Way of Communication Animal and plant cells – Have cell junctions that directly connect the cytoplasm of adjacent cells Gap Junctions: Allow small molecules to pass through animal cells. Allow cells of the same tissue to act together Plasmodesmata: in plant cells cells held together by intermediate filaments 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.

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Earl W. Sutherland – Discovered how the hormone epinephrine acts on cells – Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response

6. 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

7. 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

8. 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

9. 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

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

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ion channel receptors Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Figure 11.7 Gate closed Ions

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings TAKE HOME MESSAGE!!!!!!

13. 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

14. 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

15. 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

16. 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 – They carry the message from the membrane to the target molecule We will talk about two of them cAMP Ca+2

17. 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

18. 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

19. 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

20. 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 It plays a role in : 1. triggering muscle contractions. 2. apoptosis 3. cell adhesion to extracellular matrix 4. activation of T and B cells of the immune systemapoptosis

21. 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

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

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