1. Cell Communication Chapter 11 p. 201-217

2. Evolution of Cell Signaling There is great similarity in cell-signaling mechanisms of yeasts & mammals ▫Suggests the processes evolved very long ago Signal Transduction Pathway: process by which a signal on cell’s surface is converted into specific cellular response

3. Local & Long-Distance Signaling Some cells communicate thru direct contact w/ one another (i.e. plasmosdesmata) Local Regulators: message travels only short distance ▫Paracrine Signaling: local regulator secretes message into extracellular fluid many neighboring cells ▫Synaptic Signaling: neurotransmitters released into synapse (space between 2 cells) one target cell Long-Distance Signaling: uses hormones, released into vessels, to carry signal throughout body to target ▫Animals: endocrine signaling ▫Plants: growth regulators

4. 3 Stages of Cell Signaling: a preview 1) Reception: how target cell detects signal on membrane surface or inside cell 2) Transduction: bound signal causes changes that bring about a cellular response ▫“Signal Transduction Pathway” 3) Response: can be almost anything ▫i.e. catalysts, gene activation, etc

5. Reception: an overview Signals will only be “heard” by cells w/ specific receptor proteins ▫Signal molecule is complimentary in shape to receptor ▫Ligand: any molecule that specifically binds to another (larger) molecule  Usually causes receptor protein to change shape

6. Intracellular Receptors Located in cytoplasm or nucleus, instead of plasma membrane Signal must pass through cytoplasm of receptor cell (must be small, hydrophobic) ▫Testosterone: binds to receptor protein in cytoplasm, both enter nucleus & “turn on” genes for male sex characteristics

7. Plasma Membrane Receptors H 2 O-soluble signals bind to receptors embedded in plasma membrane ▫Receptor then transmits info inside cell by changing shape or aggregating (combining w/ 1+ other receptor proteins) 3 Types: ▫G-protein-linked receptors ▫Receptor tyrosine kinases ▫Ion channel receptors

8. G-Protein-Linked Receptors Utilizes G protein (guanosine) to carry signal from receptor enzyme further down in membrane ▫Activated enzyme triggers a cell response Consists of single polypeptide w/ 7 α helices Play role in: embryonic devlpmnt, vision, cholera, botulism ▫60% modern medicines influence G-protein pathways

10. Receptor Tyrosine Kinases Trigger more than 1 signal transduction pathway at once ▫Each may activate 10+ pathways & responses ▫Help regulate & coordinate cell growth & reproduction Kinase: an enzyme that catalyzes the transfer of phosphate groups (from ATP tyrosine) Some abnormal RTK’s can function w/out a signal, leading to cancer

12. Ion Channel Receptors Ligand-Gated Ion Channel: contains a “gated” region that allows or blocks ions from entering cell (Na +, Ca 2+ ) ▫When signal (ligand) binds, gate opens & ions enter ▫When ligand absent, gate is closed ▫Play role in nervous system (neurotransmitters act as ligands) Voltage-Gated Ion Channels: controlled by electrical signals instead of ligands

14. Transduction: an overview Usually a multi-step process to bring signal from receptor (on membrane) to target molecule (inside cell) ▫Signal may become amplified by activating multiple molecules  1 signal large response; helps coordinate & regulate processes ▫Signal itself is not relayed, but information is (conformational changes in proteins)

15. Protein Phosphorylation & Dephosphorylation Protein Kinase “on”: enzyme that transfers a phosphate group from ATP a protein ▫Usually serine or threonine (amino acids) ▫Every time a phosphate is added to the next protein, causes a conformational change (“activates” the protein) ▫Regulates proteins involved in cell reproduction (mitosis & meiosis) ▫Abnormal protein kinases may cause abnormal cell growth cancer Protein Phosphatases “off”: enzyme that removes a phosphate from proteins (“dephosphorylation”) ▫Deactivates protein & turns off signal transduction pathway ▫Makes protein kinases available to do more work

17. Second Messengers Second Messenger: small, non-protein, H2O soluble molecules or ions involved in signal transduction pathways ▫Readily spread through cell by diffusion ▫Used with G-protein-linked receptors & RTK’s ▫2 Types:  Cyclic AMP (cAMP)  Ca 2+ Ions & IP 3

18. Cyclic AMP Involved in breakdown of glycogen glucose in liver cells when epinephrine (signal) binds to G- protein-linked receptor ▫Adenylyl Cyclase: converts ATP cAMP when signal binds ▫Many cAMP made (signal is amplified) & signal is broadcasted throughout cytoplasm ▫cAMP activates protein kinase A, which phosphorylates other proteins  In cholera, bacteria modifies G protein so stays active & keeps stimulating production of cAMP  In Viagra, cGMP (cousin of cAMP) is inhibited, resulting in dilation of blood vessels

20. Ca 2+ Ions & IP 3 Involved in animal muscle contraction, secretion, cell division and in plant greening Used in G-protein-linked and RTK pathways Ca 2+ ions constantly pumped out of cytosol into ECF, ER, mitochondria, & chloroplasts ▫ [Ca 2+ ] in cytosol ▫ [Ca 2+ ] in ECF, ER, mitochondria, & chloroplast Signal IP3 (or DAG) stimulates release of Ca 2+ from ER activation of proteins response

22. Response Cytoplasmic Responses: opening/closing of ion channels in membrane, or change in cell metabolism ▫i.e.: epinephrine signals results in activation of enzyme that catalyzes glycogen breakdown Nuclear Responses: genes may be turned on/off that affect protein synthesis ▫i.e. growth factor signal results in synthesis of mRNA which will result in protein

23. Regulation of Response Signal Amplification: one signal causes large response Specificity: different cells have different proteins ▫i.e. signal, relay, & response proteins Efficiency: proteins are too large to diffuse through cytoplasm; relay would be inefficient ▫Scaffolding Proteins: hold many relay molecules in same place to increase efficiency Termination: signal molecules bind reversibly ▫When absent, receptor & relay molecules inactive & able to do more work