1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ch. 11 Cell Communication

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal transduction pathways – Convert signals on a cell’s surface into cellular responses – Are similar in microbes and mammals, suggesting an early origin 11.1 External signals are converted into responses within the cell

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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 Primitive Example in Yeast

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Quorum Sensing in Bacteria – A Vocal Majority! Cell Density can trigger bacterial behavior i.e. biolumenence & pathogenicity Avenues for new antibiotic drugs? TED talks

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local (cell-to-cell) and Long-Distance (organ-to- organ) Signaling via Chemicals Local signaling via direct contact between animal cells Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local signaling via local chemical 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

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cellular adaptations that circumvent cell membranes 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 Long-Distance signaling via hormones – Hormone: chemical messenger produced in one place but used in another – 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. Bloo d vess el Targ et cell Endocrine cell

9. 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 (adrenalin) acts on cells 3 main stages of cell signaling: – Reception – Transduction – Response

10. 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

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 11.2: Signal Reception - intracellular or plasma membrane 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

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Intracellular Receptors vs. Membrane Receptors Intracellular receptors – Are cytoplasmic or nuclear proteins There are three main types of membrane receptor proteins – G-protein-linked – Tyrosine kinases – Ion channel proteins

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings So where do signal molecules “know” where to go? Signal molecules that are small or hydrophobic – And can readily cross the plasma membrane use intracellular receptors Signal molecules that are polar/hydrophilic cannot Cross plasma membrane and therefore use membrane receptors

14. 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 Steroid hormones most common signals to enter cell Steroid hormones are non-polar and cross membrane to 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

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3 Main types of membrane receptors Type 1. G-protein-linked receptors work with GTP,GDP, GMPGDP< GMP 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

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Membrane receptor type 2 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

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Membrane Receptor type 3 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

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 11.3 Signal 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 – Transduction usually involves a conformational change in a protein shape (form/function)

19. 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

20. 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

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Role of Second Messengers in Cascades Second messengers – Are small, nonprotein, polar molecules or ions that help to conduct signal – 2 most common 2 nd messengers: cAMP, Ca 2+

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclic AMP : A Closer Look 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

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Remember G proteins? Many G-proteins trigger the formation of cAMP or cGMP, which then act as a second messengers 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 or guanylyl cyclase

24. 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 IP 3 triggers release of Ca2+ in cytosol

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Calcium Pumps EVERYWHERE! 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

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 11.4: Response via regulation of cell activities In the cytoplasm – Signaling pathways regulate a variety of cellular activities – i.e. Glycogen hydrolysis 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

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Nuclear Response (via lipid hormones) 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

28. 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

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