Unit #4: Cell Communication

1. Unit #4: Cell Communication https://www.youtube.com/watch?v=gJdjGrIGXDI https://www.youtube.com/watch?v=FkkK5lTmBYQ AP Biology Ms. Day

2. External signals  Cellular Responses • Cells useSignal transduction pathways • Convert signals OUTSIDE cell  cellular responses • Similar in microbes and mammals, suggesting an early origin

3. Why do cells use chemical signals? • To communicate without physical contact • Communication distant can be small OR large Why study cell communcation? • Allows humans to modify and change pathways, create drugs to help diseases, control diseases, agriculture production, fruit ripening, etc. What happens when cells fail to communicate properly? • Abnormal development, diseases, cancer, death

4. Chemical Signals • Cells communicate through chemical messengers • Signal molecules (ligand) • growth factors (proteins) • neurotransmitters • hormones (proteins or lipids) • peptides (small proteins) • Lipid soluble and insoluble • https://www.youtube.com/watch?v=89W6uACEb7M (14 min)

5. Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. • In local (short distance) signaling, cells may communicate via direct contact

6. Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. • Animal and plant cells • have cell junctions that directly connect the cytoplasm of adjacent cells

7. Bacteria & Cell-to-Cell Communcation • Quorum sensing (short distance communication) • Bacteria secrete chemical signal signal concentrates helps bacteria coordinate behavior • Regulation of gene expression in bacteria in response to external stimuli. • Method used in response to population density http://ed.ted.com/lessons/how-bacteria-talk-bonnie-bassler

8. 2 types of Local signaling Electrical signal along nerve cell triggers release of neurotransmitter Target cell Neurotransmitter diffuses acrosssynapse Secretory vesicle Local regulator diffuses through extracellular fluid Target cell is stimulated Synaptic signaling A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Paracrine signaling. Secreting cell acts on nearby target cells by discharging molecules of a local regulator (i.e. growth factor) into extracellular fluid. Figure 11.4 A B • Usually, multicellular organisms communicate using local regulators

9. Long-distance signaling Blood vessel Endocrine cell Hormone travels in bloodstream to target cells Target cell Animal Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. • In long-distance signaling • Both plants and animals use hormones

10. 3 Stages of Cell Signaling • https://www.dnatube.com/video/1162/Signal-transduction • https://www.youtube.com/watch?v=FtVb7r8aHco • Cells receiving signals go through3 processes • Reception • Transduction • Response

11. CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 2 3 1 Reception Transduction Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11.5 http://www.dnatube.com/video/233/The-Signal-Transduction-Pathway • Overview of cell signaling

12. STEP #1: Reception • A signal molecule binds to a receptor protein receptor changes shape • Binding between signal (calledligand) & receptorprotein is highly specific • Changing shape initiates transduction of the signal

13. Receptors • Found in “target” cells • 2 types/ locations 1. cell membrane (most abundant) called plasma membrane receptors 1st Type of Receptors

14. Plasma membrane receptors Chemical signal for these receptors can NOT pass THROUGH membrane…so it needs to be hydrophilic. WHY?

15. 2nd type of Receptors 2. inside cell called intracellular receptors • Found in cytoplasm or nucleus • Chemical signal needs to pass THROUGH membrane…so it needs to be hydrophobic. WHY?

16. Intracellular receptors (con’t) • Signal molecules that are small or hydrophobic • WHY??? • They can easily cross the plasma membrane • Ex: lipid soluble steriod/hormones (such as testosterone)

17. Specific Examples of Receptors Involved in Cell Communication

18. Hormone (testosterone) EXTRACELLULAR FLUID The steroid hormone testosterone passes through the plasma membrane. 1 Plasma membrane Testosterone binds to a receptor protein in the cytoplasm, activating it. Receptor protein 2 Hormone- receptor complex The hormone- receptor complex enters the nucleus and binds to specific genes. 3 DNA The bound protein stimulates the transcription of the gene into mRNA. mRNA 4 New protein for MALE development NUCLEUS The mRNA is translated into a specific protein. 5 CYTOPLASM Figure 11.6 http://highered.mheducation.com/sites/9834092339/student_view0/chapter9/mechanism_of_action_of_lipid-soluble_messengers.html Example #1: Intracellular receptor • Ex: Steroid hormones (lipid soluble)

19. Example #2: Membrane Receptors • There are 3 main types of membrane receptors • G-protein-linked • Tyrosine kinases • Ion channel Names based on how they work!

20. 1. G-protein-linked receptors • G-Protein = short for guanine nucleotide (GTP)-binding proteins • Ex: used in embryonic development, growth, smell, vision, over 60% of medications used today work by influencing G-protein pathways

21. G-protein-linked receptors • All G-protein-linked receptors have similar structure regardless of the organism in which they are found • Made of alpha-helices • Ligand-binding site on outside of cell • G-protein-interacting site on inside of cell • http://highered.mheducation.com/sites/9834092339/student_view0/chapter9/membrane-bound_receptors__g_proteins__and_ca2__channels.html

23. G-protein-linked receptors • Specific Example = epinephrine • http://highered.mheducation.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120109/bio48.swf::Action%20of%20Epinephrine%20on%20a%20Liver%20Cell

24. Signal-binding sitea Signalmolecule Signal molecule Helix in the Membrane Tyr Tyr Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosinekinase proteins(inactive monomers) CYTOPLASM Dimer forms Activatedrelay proteins Tyr Tyr Tyr Cellularresponse 1 Tyr Tyr Tyr P P Tyr P Tyr Tyr Tyr Tyr P Tyr Tyr Tyr P P P Tyr Tyr Tyr Tyr Tyr P Tyr Tyr Tyr Cellularresponse 2 P P P Tyr Tyr P 6 ATP 6 ADP Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) Inactiverelay proteins Figure 11.7 2. Tyrosine Kinase Receptor Ex: used cell growth and development, reproduction

25. Part of the Tyrosine Kinase receptor on cytoplasmic side serves as an enzyme • Catalyzes transfer of Pi’s from ATP to amino acid Tyrosine on substrate http://www.wiley.com/college/fob/quiz/quiz21/21-15.html https://www.youtube.com/watch?v=ObrsQl-vPA4

26. Signal molecule(ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma Membrane Gate open Cellularresponse Gate close 3. Ion channel receptors Ex: used in nervous system http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__receptors_linked_to_a_channel_protein.html

27. STEP #2: Transduction(converting the signal) • 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

28. Signal Transduction Pathways • At each step in a pathway • signal is transduced (converted) into a different form USUALLY a conformational change in a protein using… • Protein Phosphorylation and Dephosphorylation

29. In this process • protein kinases add a phosphate to the next one in line, activating it • VERY IMPORTANT ~2% of our genes • Single cell has 100’s of different kinds of kinases (substrate specific) • Think: “be kind” and give Pi’s • Phosphatase enzymesthen remove the phosphates • https://www.youtube.com/watch?v=CCDa9L7kY24

30. Signal molecule A relay molecule activates protein kinase 1. Receptor Activated relay molecule 4 1 3 5 2 Inactive protein kinase 1 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 1 Active protein kinase 2 then catalyzes the phos- phorylation (and activation) of protein kinase 3. Inactive protein kinase 2 ATP P Phosphorylation cascade ADP Active protein kinase 2 PP P i Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. Inactive protein kinase 3 ATP P ADP Active protein kinase 3 PP P i Inactive protein ATP P ADP Active protein Cellular response PP P  i A phosphorylation cascade: like a Pi relay!! Figure 11.8

31. Small Molecules and Ions act as Second Messengers • Second messengers • Are small, nonprotein, water-soluble molecules or ions Ex: cAMP (cyclic AMP), Ca2+, IP3 http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter9/second_messenger__camp.html

32. NH2 NH2 NH2 N N N N N N N N N N N O O O N O Adenylyl cyclase Phoshodiesterase CH2 O Ch2 HO P –O O P O P P O CH2 O O O O O O O O O P Pyrophosphate H2O O O P P i OH OH OH OH OH ATP Cyclic AMP AMP Figure 11.9 Cyclic AMP • Cyclic AMP (cAMP) • made from ATP by adenylyl cyclase (but cAMP is short lived!)

33. First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein GTP G-protein-linked receptor ATP cAMP Protein kinase A Cellular responses • Many G-proteins • Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways CAFFEINE BLOCKS cAMP  AMP BY INHIBITING PHOPHODIESTERASE SO cAMP LEVELS REMAIN HIGH Figure 11.10

34. Other Secondary Messagers… • Inositol triphosphate (IP3) • Triggers increase in calcium ions in the cytosol by inducing the release of Ca+2 from the ER • Calcium (Ca+2) • Ex: involved in muscle contractions

35. 3 2 1 4 6 5 A signal molecule binds to a receptor, leading to activation of phospholipase C. DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein DAG GTP PIP2 G-protein-linked receptor Phospholipase C IP3 (second messenger) IP3-gated calcium channel Cellularresponse (muscle contraction) Endoplasmic reticulum (ER) Various proteins activated Ca2+ Ca2+ (second messenger) The calcium ions activate the next protein in one or more signaling pathways. IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. Calcium ions flow out of the ER (down their con- centration gradient), raising the Ca2+ level in the cytosol. Figure 11.12

36. STEP #3: Response • Cell signaling leads to: • regulation of cytoplasmic activities or • nuclear activities • Ex: transcription • DNA  mRNA • http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter9/intracellular_receptor_model.html

37. Binding of epinephrine to G-protein-linked receptor (1 molecule) Reception Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Glucose-1-phosphate(108 molecules) Response Glycogen • Cytoplasmic response to a signal • Signal Amplification • Each protein in a signaling pathway • Amplifies (continues) signal by activating multiple copies of next component in the pathway • Can be many or few proteins in cascasde Figure 11.13

38. Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gene mRNA NUCLEUS Figure 11.14 • Other pathways • Regulate genes by activating transcription factors that turn genes on or off http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter9/how_intracellular_receptors_regulate_gene_transcription.html NOTE: Transcription is DNA  mRNA

39. Signalmolecule Receptor Relaymolecules Response 1 Response 2 Response 3 Cell B. Pathway branches, leading to two responses Cell A. Pathway leads to a single response Activationor inhibition Figure 11.15 Response 4 Response 5 Cell C. Cross-talk occurs between two pathways Cell D. Different receptor leads to a different response • Pathway branching and “cross-talk” • Further help the cell coordinate incoming signals

40. Signalmolecule Plasmamembrane Receptor Threedifferentproteinkinases Scaffoldingprotein Figure 11.16 Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins • Can increase the signal transduction efficiency

41. Termination of the Signal • Signal response is terminated quickly • By the reversal of ligand binding ACTIVE- TURNED “ON” INACTIVE- TURNED “OFF”

42. When things go wrong… • Diabetes • Heart disease • Neurological or autoimmune disorders • Cancer • Death (ex: from neurotoxins, poisons, pesticides)

43. Overall Signal Transduction Pathway…explained  • https://www.youtube.com/watch?v=qOVkedxDqQo&feature=youtu.be

44. Evolutionary Significance of Cell Communication • https://www.youtube.com/watch?v=FsGwgiIv_NU&feature=youtu.be

45. Effects of Changes in Pathways • https://www.youtube.com/watch?v=W48Gk2Om3wI&feature=youtu.be

46. Great tutorial to use to study… • https://www.youtube.com/watch?v=qOVkedxDqQo&feature=youtu.be • http://www.biology.arizona.edu/CELL_BIO/problem_sets/signaling/04q.html

47. Cholera • Affects a G linked protein reception in the cells lining the intestines • Toxin from contaminated water causes this • Turns ON the signal permanently • (cAMP) not broken down • Causes water imbalance  leads to diarrhea and perhaps DEATH!!!