Cell Communication

1. Cell Communication

2. The “Cellular Internet” • All multicellular organisms must “communicate and cooperate” to maintain homeostasis • universal mechanisms of cellular regulation involve cell-to-cell communication. • Basically, a signal is received and then converted into a response within the cell

3. Methods used by Cells to Communicate • Cell Signaling using chemical messengers (proteins, steroids, etc) • Local signaling over short distances • Cell-Cell Recognition Proteins attached to cell exterior; glycolipids and glycoproteins (e.g. blood type proteins) • Local regulators (chem signals from the neighboring cells) • Paracrine- secreted signal (e.g. growth factors) • Synaptic- directed signal (e.g.neurotransmitter) • Long distance signaling • Hormones - ENDOCRINE

4. 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. Cell-Cell Communication • Transport between cells • cell junctions are protein tunnels directly connecting adjacent cells (called gap junctions in animal cells & plasmodesmata in plants); allow material to pass through (e.g. chem signals or water)

5. Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. Local Signaling Example: Cell-Cell Recognition • Used to guard against unfamiliar cells and invaders; part of immune response • Membrane bound cell surface molecules • Glycoproteins • Glyolipids

6. Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses acrosssynapse Secretory vesicle Local regulator diffuses through extracellular fluid Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. (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. Local Signaling Example: Local Regulators - Communicate with neighbors using local regulators, only work over a short distance - Paracrine signaling communicates with all cells surrounding (e.g. growth factor to stimulate mitosis near a wound) - Synaptic signaling is directed to one neighbor cell (e.g. neurotransmitters from one neuron to the next)

7. Long-distance signaling Blood vessel Endocrine cell Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Figure 11.4 C Long-distance Signaling Example: Hormones • long-distance signaling used by both plants and animals; hormones (natural steroids) are released into bloodstream by glands and can go anywhere in the body causes changes in a lot of cells simultaneously (e.g. adrenaline)

8. Long-Distance Signaling Systems • Nervous System (Animals only) • Quick long distance communication through Electrical signals sent through neurons • Endocrine System (Animals only) • Glands that secrete hormones into cell spaces or into blood stream (lymph nodes, adrenal gland, pituitary gland, etc) • Note: Plants also use hormones • Transported through vascular system, plasmodesmata, or released into air (e.g. ripening fruit)

9. The Three Stages of Cell Signaling • All cell signaling (long or short distance) occurs in three stages • Reception – receive the signal • Transduction – signal causes a cascade of communication inside the cell • Response – cell responds to the signal • Called Signal transduction pathways • Note: Pathways are similar in all life, supporting evolution

10. EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 2 3 Reception Transduction Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11.5 Overview of cell signaling

11. Stage One: Reception • The signaling molecule (a ligand) binds to the specific receptor protein; shape determines function! CYTOPLASM EXTRACELLULAR FLUID Plasma membrane Reception 1 1 The receptor and signaling molecules fit together (lock and key model, induced fit model, just like enzymes!) Receptor Signaling molecule

12. Stage Two: Transduction CYTOPLASM EXTRACELLULAR FLUID Plasma membrane Reception Transduction 1 1 2 Receptor 2nd Messenger! Relay molecules in a signal transduction pathway Signaling molecule • Reception sets off a relay team of communication proteins in the cell; second messengers carry the original exterior signal to the inside of the cell

13. Stage Three: Response CYTOPLASM EXTRACELLULAR FLUID Plasma membrane Reception Transduction Response 1 2 3 Receptor Activation of cellular response Relay molecules in a signal transduction pathway Can be catalysis, activation of a gene, triggering apoptosis, almost anything! Signaling molecule • The cell will respond to the signal as directed (e.g. make a protein, produce more energy, enter mitosis, etc.)

14. Signal Transduction Animation http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&A http://www.wiley.com/legacy/college/boyer/0470003790/animations/signal_transduction/signal_transduction.htm

15. Common Receptor Proteins (stage one) G-protein coupled receptors Receptor tyrosine-kinases Ion channel receptors

16. G-Protein Coupled Receptors are often involved in diseases such as bacterial infections. G-Protein Receptors Inactive enzyme Plasma membrane G protein-coupled receptor Activated receptor Signaling molecule Enzyme GDP 2 1 GDP GTP CYTOPLASM G protein (inactive) Activated enzyme i GTP GDP P 4 3 Cellular response

17. Signal-binding site 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) Dimer CYTOPLASM Activatedrelay proteins Cellularresponse 1 Tyr Tyr Tyr 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 Receptor tyrosine kinases

18. Ion Channel Receptors Gate closed 1 Ions Signaling molecule (ligand) • Very important in the nervous system • Creates an action potential • Signal triggers the opening of an ion channel • Opening the channel allows ions to rush down a concentration gradient, creating an electrical signal from the moving charges Ligand-gated ion channel receptor Plasma membrane 2 Gate open Cellular response 3 Gate closed

19. Notes about Transduction • Reminder, Transduction is the second stage. It occurs when cascades of molecular interactions relay signals from the receptor to the target molecules inside the cell • It is a multistep pathway • can amplify a signal and create a large response from a single ligand • Requires communication and coordination within the cell itself • Transduction Example: Protein Phosphorylation

20. Protein Phosphorylation and Dephosphorylation • Protein Phosyphorylation cascade - An example of transduction in which a series of protein kinases add a phosphate to the next one in line, activating it, and sending the signal to the target (like a bucket brigade!) • enzymes then remove the phosphates to reset the cascade after “Response” stage

21. 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 Phosphorylation cascade P Active protein kinase 2 ADP 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. Inactive protein kinase 3 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 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 Figure 11.8

22. Small Molecules and Ions as Second Messengers • Transduction Example: • Secondary messengers: small, nonprotein, water-soluble molecules or ions that act as secondary messengers to carry the signal to the target (example- cyclic AMP) • (Note: Membrane Proteins would be the primary messengers since they get the signal first)

23. First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein GTP G-protein-linked receptor ATP cAMP Protein kinase A Cellular responses Cyclic AMP • cAMP is often found with the G-protein receptors; made from ATP that has only one phosphate; secondary messenger Figure 11.10

24. NH2 NH2 NH2 N N N N N N N N N N N O O O N O Adenylyl cyclase Phoshodiesterase CH2 O HO Ch2 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 Cyclic AMP • Cyclic AMP (cAMP) • Is made from ATP

25. First messenger Adenylyl cyclase G protein Fig. 11-11 GTP G protein-coupled receptor ATP Second messenger cAMP Ex Diagram: Transduction in a G-protein pathway using cAMP Protein kinase A Cellular responses

26. EXTRACELLULAR FLUID Plasma membrane Ca2+pump ATP Mitochondrion Nucleus CYTOSOL Ca2+pump Endoplasmic reticulum (ER) ATP Ca2+pump Key High [Ca2+] Low [Ca2+] Second Messenger Example: Calcium Ions • Calcium ions act as a secondary messenger in many different pathways because cells can regulate its concentration and location Other secondary messengers trigger the release of concentration gradients of Ca2+ in various areas of the cell, creating moving charges and electrical signals. Pumps then reset the Ca2+ concentration gradient to be used again.

27. 6 3 2 1 4 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 Endoplasmic reticulum (ER) Various proteins activated Cellularresponse 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. Calcium Ion Diagram example Figure 11.12

28. Signaling molecule • Cellular Response (Stage 3) • Specificity of the signal • The same signal molecule can trigger different responses depending on other signals and various receptor proteins or SMs • Many responses can come from one signal! Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.

29. The signal can also activate, inhibit ,or create multiple responses from one signal Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

30. Response example- cell signaling leads to regulation of transcription (turn genes on or off)

31. Long-distance Signaling Response Example Some hormones induce transcription. Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated. (ex: testosterone, which is a transcription factor)

32. Termination of Communication • Response is terminated quickly by the reversal of ligand binding

33. Any Questions?? Can You Hear Me Now?

34. Two body systems control MOST communication 1. Nervous System– uses ion concentration gradients and action potentials to communicate quickly through electrical impulses and neurons 2. Endocrine System - uses hormones secreted into the bloodstream (faster, further reach) or surrounding cell space; slower than nervous system, but longer lasting effect

35. Cell Communication/Signaling • This is an extremely important part of understanding how an organism actually maintains homeostasis and survives. • View Page 55 in your Test Prep book (Look @ YOU MUST KNOW) section. Make sure you have these written down and have notes to address each of them. • DNA LEARNING CENTER ANIMATION link • Bozeman videos, #37, #38, #39 and #32 all explain and give examples of Cell Signaling and WHAT Happens if it goes WRONG! • KHAN ACADEMY simplifies CELL COMMUNICATION using basic terminology

36. Human Endocrine System

37. Major Vertebrate Endocrine Glands Their Hormones (Hypothalamus–Parathyroid glands)

39. Neurosecretory cells in endocrine organs and tissues secrete hormones. These hormones are excreted into the circulatory system (ex. Adrenaline) or the surrounding cell space (ex. Lymph).

40. Are the following hormone pathways Positive or Negative Feedback systems? Stress and the Adrenal Gland http://highered.mcgraw-hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120109/bio48.swf::Action%20of%20Epinephrine%20on%20a%20Liver%20Cell

41. http://bcs.whfreeman.com/thelifewire/content/chp42/4202003.htmlhttp://bcs.whfreeman.com/thelifewire/content/chp42/4202003.html

42. http://vcell.ndsu.nodak.edu/animations/regulatedsecretion/movie.htmhttp://vcell.ndsu.nodak.edu/animations/regulatedsecretion/movie.htm

43. Answers • Stress and Adrenaline – Positive Feedback (induces a response/change) • Calcium and Blood Sugar regulation – Negative Feedback (prevents a change, maintains a normal level)