1. Cell Communication
Chapter 11 p

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. Local Signaling
Direct Contact
Local
Regulators

5. 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

6. 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

7. 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

8. Plasma Membrane Receptors
H2O-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

9. 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

11. 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

13. Ion Channel Receptors
Ligand-Gated Ion Channel: contains a “gated” region that allows or blocks ions from entering cell (Na+, Ca2+)
When signal (ligand) binds, gate opens & ions enter
When ligand absent, gate is closed
Play role in nervous system (neurotransmitters act as ligands) and muscle contraction
Voltage-Gated Ion Channels: controlled by electrical signals instead of ligands

15. 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)

16. 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

18. 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)
Ca2+ Ions & IP3

19. 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

21. Ca2+ Ions & IP3
Involved in animal muscle contraction, secretion, cell division and in plant greening
Used in G-protein-linked and RTK pathways
Ca2+ ions constantly pumped out of cytosol into ECF, ER, mitochondria, & chloroplasts
[Ca2+] in cytosol
[Ca2+] in ECF, ER, mitochondria, & chloroplast
Signal IP3 (or DAG) stimulates release of Ca2+ from ER activation of proteins response

24. 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

25. 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