1. Chapter 11: Cell Communication

2. Word Roots:
liga- = bound or tied to
trans- = across
Ligand – a small molecule that specifically binds to a larger one.
Transduction – the transmission of external signals and conversion of a message inside of the cell

3. Signal Transduction Pathways
Local Signaling
Direct contact
Cell junctions
Local Regulators
Paracrine signaling
Synaptic signaling
Long Distance Signaling
Hormones
Nervous

4. Direct Contact
Cell to cell recognition – embryonic development and immune respose

5. Evolution of Cell Signaling
Yeast cells
Identify their mates by cell signaling
 factor
Receptor
Exchange of mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type. 1
Mating. Binding
of the factors to
    receptors
induces changes
     in the cells that
    lead to their
    fusion.
New a/ cell.
The nucleus of
the fused cell
includes all the
genes from the
a and a cells. 2 3
Yeast cell,
mating type a
mating type  
a/ a
Figure 11.2
Similar cellular communication in yeast (Fungi) and mammals even though the last common ancestor of these two groups of organisms lived over a billion years ago. Similarities have also been found between plants and bacteria.

6. Local Signaling Less specific Growth factors More Specific
Growth factors stimulate local cells to grow and multiply. The signal can be sent to and received by multiple cells.
Nerve cell triggers the secretion of a neurotransmitter – seen in animal nervous systems
Less specific
Growth factors
More Specific
Neurotransmitters

7. Long Distance Signaling
Very Specific
Target specific cells
Hormones (endocrine signaling)
Nerves – electrical transmission of impulses
Plants use long distance signaling – ex: growth regulators that travel is vessels – hormone ethylene, a gas that promotes fruit ripening and regulation of growth is small and can pass through cell walls.
Mammilian hormone insulin, regulates sugar levels in the blood, is a large protein of a thousand atoms.

8. Three Stages of Cell Signaling
Earl W. Sutherland – 1971
Signal Transduction Pathway for glycogen breakdown.
Reception
Target cell detects a signal molecule from outside the cell when a ligand binds to a receptor
Transduction
binding of signal molecule changes the shape of the receptor initiating transduction  sequence of changes in a series of molecules
Response
Transduced signal triggers a specific cellular response
Ex: catalysis of enzyme, activation of genes, etc..

9. Three Stages of Cell Signaling

10. Step 1: Reception Receptor Protein (conformational change) Membrane
Cytoplasm
Nucleus
Signal Molecule
Ligand (highly specific)
Small/hydrophobic
Ex: steroid hormones
Large/water soluble
Ex: epinepherine

11. A hydrophobic ligand can readily cross the plasma membrane and bind to an intracellular receptor
Testosterone acts as a transcription factor

12. Three Main Types of Plasma Membrane Receptors
G-Protein Linked
Receptor Tyrosine Kinases
Ion Channel

13. Ex: Fight or Flight Response
G-Protein Linked
Ex: Fight or Flight Response
Reception: Epinepherine targets liver and muscle cells
Transduction: activates glycogen phosphorylase
Response: break down glycogen into glucose

14. G-Protein Linked
Embryonic development, sensory reception, yeast mating factors, epinepherine, many other hormones and neurotransmitters
GTP – guanosine triphosphate (a nucleiotide)
GDP
GTP
Ligand binding  receptor shape change inactive G protein binds  GTP replaces GDP  activating the G protein
Inactive G protein
Adenylyl cyclase
Sensory in humans such as vision and smell
G-protein diseases – bacterial infections – cholera, pertussis (whooping cough), and botulism - make their victims ill by producing toxins that interfere with G-protein function
60% of medications exert their effects by influincing G protein receptors
GTP
GDP Pi
Signal transduction pathway initiated
Activated G protein dissociates from the receptor  binds to an enzyme and alters its activity  triggering the next step in the pathway
G protein acts as GTPase  hydrolyzing GTP into inactive GDP  shutting down pathway when ligan is not present

15. Receptor Tyrosine Kinases
Kinase – enzyme that catalyzes the transfer of a phosphate group
Tyrosine kinase – membrane receptors that attach phosphates to the amino acid, tyrosine
Regulates growth and reproduction
Multiple pathways stimulated
Branched pathways (10+)
Abnormal receptor tyrosine kinases may contribute to some kinds of cancer

16. Receptor Tyrosine Kinases
Example is a growth factor binding to a tyrosine kinase
Dimerization activates the tyrosine kinase region of each polypeptide each tyrosine kinase adds a phosphate from ATP to a tyrosine amino acid on the tail of the other polypeptide

17. Ion Channel Receptors Ligand-gated ion channels Nervous system
Sodium –Potassium Pump
Some channels are controlled by electrical signals instead of a ligand
Na+ and Ca2+
Na+ gates open during depolarization of a neuron
Ca gates open when the impulse reaches it and the Ca influx causes the release of the neurotransmitters

18. Sodium Potassium Pump

19. Checkpoint
Compare and contrast the three major types of membrane receptors.

20. Step 2: Transduction Multi-step
Amplifies signal – signal sent to multiple molecules
Require Relay Molecules
Protein Kinases – transfers phosphate groups from ATP to a protein
Serine/threonine kinases (animals, plants, fungi)
Phosphorylation cascade
Conformational change
Increase or decrease activity of the protein
Protein Phosphatases – remove phosphates from proteins
Recycle and reuse kinases (dephosphorylation)

21. Reception
Transduction
Phosphorylation Cascade
Response

22. Second Messengers Small, non-protein, water soluble molecules or ions
Diffuse easily
Easily Amplified
Cyclic AMP (cAMP)
Calcium ions (Ca2+)
Inositol triphosphate (IP3)
Diacylglycerol (DAG)

23. Cyclic AMP Cyclic adenosine monophosphate
Created by Adenylyl Cyclase from ATP
Many cAMP molecules – amplification
Phosphodiesterase
Activates Protein Kinase A

24. Cholera – a disease where water is contaminated with human feces
Cholera – a disease where water is contaminated with human feces. Bacteria colonize in small intestines and produce a toxin. This toxin modifies the g protein that regulates salt and water secretion.G protein is unable to hydrolyze GTP into GDP and its stuck in its active form, continuously activating adenylyl cyclase to continue to make cAMP. An infected person develops severe diarrhea. Causes intestinal cells to continue to secret water.

25. ‘Locking’ the pathway Cholera – Vibrio cholerae
Locks G-Protein for water and salt regulation ‘on’
Unable to hydrolyze GTP into GDP = stuck in active form
Diarrhea
Vasodilatation
Cyclic GMP – relaxes artery walls
Viagra – blocks cyclic cGMP from breaking down into GMP
– increases blood flow, prolonging the signal

26. Calcium Ions and Inositol Triphosphate
Ca2+ low in cytosol, high in ER and ECF
Active transport and membrane proteins
Controlled by gated ion channels
Regulates:
Muscle contraction
Secretion of other substances
Cell division
Used:
G-protein
Receptor Tyrosine Kinases

29. Step 3: Response Cytoplasmic or Nuclear Regulates:
Enzyme/Protein activity
Enzyme/Protein creation
Transcription factors
Growth factors
Hormones

30. Cytoplasmic Response

31. Nuclear Response

32. Benefits of Transduction Pathways
Signal Amplification
Each step – more amplification
Specificity
Branched pathways – Receptor Tyrosine Kinases

33. Signaling Efficiency Scaffolding Proteins Signaling Complexes
Proteins can participate in:
More than one pathway in 1 cell
Many pathways in different cells

34. Step 4: Signal Termination
Reversible binding
Signal molecule unbinds
GTPase activity
Phosphodiesterase
Phosphatases