1. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Chapter 11 Cell Communication

2. Overview: The Cellular Internet Cell-to-cell communication is essential for multicellular organisms. Biologists have discovered some universal mechanisms of cellular regulation. The combined effects of multiple signals determine cell response. For example, the dilation of blood vessels is controlled by multiple molecules. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

3. Evolution of Cell Signaling A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response. Signal transduction pathways convert signals on a cell’s surface into cellular responses. Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes. The concentration of signaling molecules allows bacteria to detect population density. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

4. Local and Long-Distance Signaling Cells in a multicellular organism communicate by chemical messengers. Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells. In local signaling, animal cells may communicate by direct contact, or cell-cell recognition. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

5. Cell Signaling Plasma membranes Gap junctions between animal cells (a) Cell junctions Plasmodesmata between plant cells (b) Cell-cell recognition

6. In many other cases, animal cells communicate short distances using local regulators, messenger molecules that travel only. In long-distance signaling, plants and animals use chemicals called hormones delivered via the blood. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

7. Local and Long-Distance Signaling Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling (b) Synaptic signaling Target cell is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

8. The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine acts on cells. Sutherland suggested that cells receiving signals went through three processes: – Reception – Transduction (relay / cascade … amplifies) – Response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

9. Signal Transduction Pathway EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule: ligand Relay molecules in a signal transduction pathway Activation of cellular response Transduction Amplification of signal Response 2 3 Reception 1

10. Protein Receptors in the Plasma Membrane Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane. There are three main types of membrane receptors: – G protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

11. Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1

12. Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves multiple steps. The molecules that relay a signal from receptor to response are mostly proteins. Multistep pathways can amplify a signal: A few molecules can produce a large cellular response. Multistep pathways provide more opportunities for coordination and regulation of the cellular response. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

13. Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P P PP Inactive protein kinase 3 ATP ADP Active protein kinase 3 P P PP i ATP ADP P Active protein PP P i Inactive protein Cellular response Phosphorylation cascade i Amplification -- Cascade

14. Small Molecules and Ions as Second Messengers The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger.” Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion. Cyclic AMP and calcium ions are common second messengers. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

15. Calcium Ions -- Second Messengers Calcium ions (Ca 2+ ) act as a second messenger in many pathways. Calcium is an important second messenger because cells can regulate its concentration. A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

16. EXTRACELLULAR FLUID Ca+ Ions as Second Messengers ATP Nucleus Mitochondrion Ca 2+ pump Plasma membrane CYTOSOL Ca 2+ pump Endoplasmic reticulum (ER) Ca 2+ pump ATP Key High [Ca 2+ ] Low [Ca 2+ ]

17. Calcium and IP 3 in signaling pathways G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Various proteins activated Cellular responses Ca 2+ (second messenger ) GTP

18. Nuclear and Cytoplasmic Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities. The response may occur in the cytoplasm or may involve action in the nucleus. Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus. The final activated molecule may function as a transcription factor. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

19. Nuclear responses to a signal: the activation of a specific gene by a growth factor Growth factor Receptor Phosphorylation cascade Reception Transduction Active transcription factor Response P Inactive transcription factor CYTOPLASM DNA NUCLEUS mRNA Gene

20. Other signaling pathways regulate the activity of enzymes. Signaling pathways can also affect the physical characteristics of a cell, for example, cell shape. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

21. Fine-Tuning of the Response Signal Transduction multi-step pathways have two important benefits: – Amplifying the signal (and thus the response) – Contributing to the specificity of the response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

22. Signal Amplification Enzyme cascades amplify the cell’s response. At each step, the number of activated products is much greater than in the preceding step. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

23. The Specificity of Cell Signaling and Coordination of the Response Different kinds of cells have different collections of proteins. These different proteins allow cells to detect and respond to different signals. Even the same signal can have different effects in cells with different proteins and pathways. Pathway branching and “cross-talk” further help the cell coordinate incoming signals. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

24. Specificity of Cell Signaling Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Response 4 Response 5 Activation or inhibition Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

25. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Scaffolding proteins are large relay proteins to which other relay proteins are attached. Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

26. Termination of the Signal Inactivation mechanisms are an essential aspect of cell signaling. When signal molecules leave the receptor, the receptor returns to its inactive state. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

27. Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide. Apoptosis can be triggered by: – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum. For example, apoptosis in the cells that form webbing between fetal human fingers and toes is a normal part of development. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

28. Review: Signal Transduction Pathway Reception Transduction Response Receptor Relay molecules Signaling molecule Activation of cellular response 1 2 3

29. You should now be able to: 1.Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system. 2.List two advantages of a multistep pathway in the transduction stage of cell signaling. 3.Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

30. 4. Define the term second messenger ; briefly describe the role of these molecules in signaling pathways. 5. Explain why different types of cells may respond differently to the same signal molecule. 6. Describe the role of apoptosis in normal development. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings