1. Cell Communication

2. Types of Cell Communication
Cells in multicellular organisms communicate via chemical messages
Local (cells are adjacent)
Long-distance
Specific target cells recognize and respond to a specific signaling molecule

3. Local Cell Communication
Cells that are adjacent may communicate via
Cell Junctions – molecules pass via the cytoplasm using cell junctions between cells (plant and animal cells)
Cell-cell recognition – Communication by interaction of molecules protruding from the surface of the cells (Animal)

4. Local Cell Communication
Cells that are near each other, but not necessarily adjacent may also communicate via
Paracrine Signaling – A secreting cell acts on nearby target cells by discharging ‘messenger’ molecules of a local regulator into the extracellular fluid (for example: growth factor)
Synaptic Signaling – A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell

5. Long-Distant Cell Communication
At times a signal cell and target cell are farther apart
Hormonal/Endocrine Signaling – Specialized cells release hormone molecules that travel via the circulatory system to the target cells
Plants use similar system using vessels or diffusion as travel
The nervous system can also be considered a part of long-distance communication

6. Stages of Cell Signaling
Reception
Transduction
Response

7. Reception
A receptor protein on or near the target cell allows the cell to detect and react to messages
The signaling molecule is complimentary in shape and site specific on the receptor molecule
Ligand (molecule that specifically binds to another) binding generally causes a receptor protein to change shape and may cause activation of the receptor
Causes the combining of 2 or more receptor molecules, leading to other molecular events

8. Types of Receptors Plasma Membrane Receptors
Most are water-soluble and embedded in the cell membrane
Transmits info from extracellular environs to inside the cell via shape change or aggregation
Examples: G protein-coupled receptors, receptor tyrosine kinases, ion channel receptors

9. G Protein-Coupled Receptors
Composed of seven α helices that span the plasma membrane with loops that act as binding sites
Binds energy-rich GTP
Functions include: role in embryonic development, sensory reception (vision and smell)
Involved in many bacterial diseases (Ex: Cholera)
Toxins produced by these diseases interfere with the G protein
Many medicines also interact with G protein pathways

10. G Protein-Coupled Receptors
G protein functions as an ‘on/off’ switch for the molecule depending on whether GDP (inactive) or GTP (active) is attached
Signaling molecule causes a shape change. The cytoplasmic side binds to the G protein, causing a GDP to be displaced by a GTP, activating the molecule.
Activated G protein then binds to an enzyme, triggering the next step in a pathway.
GTP is hydrolyzed, creating GDP and leaving the G protein inactive

11. Receptor Tyrosine Kinases
Receptors begin as individual polypeptides with ligand binding sites
The binding of a signaling molecule causes the polypeptides to associate creating a dimer and activating the tyrosine kinase region
Each tyrosine kinase adds a P from ATP, fully activating the receptor protein
Specific relay proteins will now bind to specific phosphorylated tyrosine, causing a structural change activating the bound proteins and triggering a transduction pathway

12. Ion Channel Receptors
Gate on an ion channel remains closed until a ligand binds to the receptor
Specific ions can flow through when gate opens, rapidly changing the concentration of those ions inside the cell
Ligand dissociates from the receptor closing the gate

13. Types of Receptors Intracellular Receptors
Found in either the cytoplasm or nucleus of target cells
A chemical messenger will need to pass through the plasma membrane
Tend to be either hydrophobic or small enough to cross
Examples: Steroid Hormones, Thyroid Hormones, nitric oxide

14. Steroid Hormone
Testosterone passes through the cell membrane, binds with the receptor molecule becoming active.
The active form then enters the nucleus and turns on specific genes that control male sex characteristics
Transcription factors – control which genes are turned on (transcribed into mRNA)

15. Transduction
Binding of the signaling molecule changes the receptor protein and initiates transduction
May involve a single step, but more often is a sequence of steps in a pathway
For plasma membrane receptors this is usually a multistep pathway
May include activation of proteins by addition or removal of phosphate groups or release of ions or small molecules
Multiple steps allows for amplification, greater coordination and regulation of the signal

16. Signal Transduction Pathways
The binding of a signaling molecule begins the pathway with each step leading to another step and eventually leading to a cellular response
Protein kinase is a relay molecule and is used to pass a P molecule from ATP to a protein
Several protein kinases may act on each other in a chain or phosphorylation cascade
Enzymes called protein phosphatases rapidly remove P groups from proteins, inactivating proteins and turning off the pathway
Signal Transduction Pathways

17. Ions and Molecules as 2nd Messengers
Signal transduction pathways will sometimes involve nonprotein molecules that are water-soluble or ions called 2nd messengers
Can readily spread throughout the cell via diffusion
Examples: Cyclic AMP, Calcium ions and IP3

18. Cyclic AMP Cyclic adenosine monophosphate (cAMP)
An enzyme (adenylyl cyclase) in the plasma membrane converts ATP to cAMP in response to a signal (first messenger)
cAMP broadcasts the signal to the cytoplasm, usually activating protein kinase A which phosphorylates other proteins
Example: Epinephrine

19. Calcium Ions and IP3 More commonly used than cAMP
Signal induces an increase in cytosolic concentration of Ca2+
Concentration usually much higher outside of cell and within certain organelles (ER, mitochondria, chloroplasts)
Rise in CA2+ usually accomplished by release of calcium from ER
Causes muscle cell contraction, cell division, secretion of substances
Used by neurotransmitters, growth factors and some hormones
Inositol triphosphate (IP3) and diacylglycerol (DAG) are other 2nd messengers

20. Response
The final outcome of the message which is the regulation of some cellular activity
Response may occur in cytoplasm or nucleus, but many regulate protein synthesis by turning specific genes on and off

21. Fine-Tuning the Response
Signal Amplification
Specificity of Cell Signaling and Coordination of the Response
Pathway leads to a single response
Pathway branches leading to two responses
Cross-talk occurs between 2 pathways
Different receptor leads to a different response
Signaling Efficiency
May be related to the presence of scaffolding proteins that hold several relay proteins which may help to hold pathways together
Termination of Signal

22. Apoptosis Programmed cell suicide
Occurs when cells are infected, damaged or old/beyond cell usefulness
Signals for death may come from outside the cell or via alarms inside
Alarms come from either the nucleus (DNA has suffered irreparable damage) or the ER (excessive protein misfolds)
DNA is chopped up, organelles are fragmented, and the cell shrinks and goes through blebbing (becomes lobed)
The cells parts are then packaged up into vesicles and are digested by scavenger cells