1. Chapter 11 Cell Communication

2. Cell Signaling All cells communicate
Prokaryotes: first organisms to use signaling
Animal cells communicate by:
1. Direct contact (gap junctions)
2. Local regulators (growth factors, neurotransmitters)
3. Long distance (hormones)

3. Local vs Long Distance Signaling
Local regulators – affect only nearby cells Paracrine signaling – cells release chemicals to nearby cells Neurotransmitters released from neurons Direct Contact – between immune cells Long distance- affect distant cells (hormones) Endocrine signaling – chemicals released into blood and carried throughout body How Cells Talk - Need correct receptors - Either inside cell or along cell membrane

4. Communication by Direct Contact
Cells can also pass messages directly
Cell Junctions (directly connect cytoplasm of connecting cells
Gap junctions
ex: cardiac cells- rhythm
Plasmodesmata
Surface receptors
(Cell to Cell recognition)
“ID tag” recognition
Cell markers
Immune responses

5. Basic Stages of Cell Signaling
Signal Transduction Pathway (STP) : steps involved in passing along message to cause cellular effect
1. Reception: Detection of a signal molecule (ligand) coming from outside the cell
- causes change in shape of receptor protein
Transduction: Convert signal to a form that can bring about a cellular response
Response: Cell takes action in response to the signal molecule

6. Step 1: Reception
Chemical signal (ligand) binds to very specific receptor
- causes receptor to change shape
Types of Receptors
Plasma membrane receptor
Hydrophilic or large ligands
Intracellular receptors (cytoplasm, nucleus)
hydrophobic or small ligands
ex: testosterone

7. Step 1: Reception
Most signal receptors are proteins on the plasma membrane
4 types:
G-Protein Coupled Receptors (GPCP)
- most common, over 1000
Tyrosine-Kinase Receptors
Ion-Channel Receptors
Intracellular Receptors

8. Reception: Protein Receptors
G Protein-Coupled Receptor (GPCR)
G-proteins use GTP (not ATP)
Functions
Embryonic development
Sensory reception
Hormones and neurotransmitters
Involved in human diseases and bacterial infections that produce toxins that interfere with G protein functions
~60% of medicines affect G protein pathways

9. Reception: Protein Receptors
G Protein – Coupled Receptor (GPCR)
Signal binds to receptor  G-protein activated  enzyme is activated  cellular response

10. Reception: Protein Receptors
Receptor Tyrosine- Kinase (RTK)
Receptors that attach phosphates to tyrosines
Have enzyme activity
Receptor on membrane, tail in cytoplasm
Kinase: catalyzes transfer of phosphates
When receptors get signal,
they form a “dimer”
(two parts come together)
Protein (enzyme) pulls
PO4 off ATP & adds it to
tyrosines on “tail” portion
They become activated
Message is now relayed to
nearby proteins
Continues the signaling
chain-reaction

11. Reception: Protein Receptors
RTKs (continued)
Single ligand binding event triggers many pathways
May activate 10+ pathways and cellular responses
Coordinates cell growth and reproduction
Abnormal RTKs associated with HER 2 breast cancer
Too many receptors push cancer cell growth

12. Reception: Protein Receptors
Ion Channel Receptors
Ligand Gated Ion Channel
Regulates flow of ions thru cell
Chemical signal binds to
protein channel changing its
shape
Channel opens/closes
Allows/blocks specific ions
(Na, Ca)
Found in synapses between
nerve cells

13. Reception: Protein Receptors
Plasma Membrane Receptors Review
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
7 transmembrane segments in membrane
Attaches (P) to tyrosine
Signal on receptor changes shape
G protein + GTP activates enzyme  cell response
Activate multiple cellular responses at once
Regulate flow of specific ions
(Ca2+, Na+)

14. Intracellular Protein Receptors
Some receptors are in cytoplasm
or nucleus of target cell
(instead of along membrane)
Chemical messenger must pass through plasma membrane and
activates receptor protein
Small or hydrophobic
ex: steroids
testosterone acts as
transcription factor- turns on
genes to control male sex characteristics

15. What determines whether a signal will bind to a membrane protein or an intracellular protein? Membrane signals – cannot get through Large – polar – ionic Intracellular signals – can get through Hydrophobic - small

16. Which types of cells communicate this way. Most of them
Which types of cells communicate this way? Most of them! bacteria – yeast (fungi) – plants - animals

17. Step 2: Transduction
Passing of message - signal molecule not passed along- only message - usually involves changes in the molecules doing the passing due to phosphoryation - relay molecules are proteins - Signal transduction pathway: triggered by reception

18. Transduction Phosphorylation Cascade
Each protein activates next by phosphorylating it
Causes cascades of molecular interactions relay signals from receptors  target molecules
Last step involves activating protein to cause cellular effect
Protein kinase: enzyme that
phosphorylates and
activates proteins at next level
’s in cells
- cascade enhances and amplifies signal
Protein phosphatases:
enzymes that dephosphorylate
(inactivate) proteins
- turns of STP

19. Transduction: Second Messengers
Molecules in cytoplasm that receive signal and relay message at accelerated rate (yelling thru window)
small, non-protein hydrophilic molecules/ions
spread by diffusion
initiated by GPCRs and RTKs (1st messengers)
faster than hydrophobic messengers- does not require as much signal chemical to produced
ex: cyclic AMP (cAMP), calcium ions (Ca2+), inositol triphosphate (IP3)

20. Transduction: Second Messengers
cAMP = cyclic adenosine monophosphate
How it works
- 1st messenger activates GPCR
- G protein adenylyl cyclase S
converts ATP to cAMP
- cAMP broadcasts signal to
cytoplasm
- activates protein kinase A
leads to cellular response
**G proteins can be activators or
inhibitors to regulate systems*

21. Transduction: Second Messengers
Calcium Ions and Inositol P3 (IP3)
Both used in both G protein and RTK pathways
Used in muscle cell contraction, secretion, cell division 3 2 1
IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open. 4
The calcium ions
activate the next
protein in one or more
signaling pathways. 6
Calcium ions flow out of
the ER (down their con-
centration gradient), raising
the Ca2+ level in the cytosol. 5
DAG functions as
a second messenger
in other pathways.
Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRA-
CELLULAR
FLUID
Signal molecule
(first messenger)
G protein
G-protein-linked
receptor
Various
proteins
activated
Endoplasmic
reticulum (ER)
Phospholipase C
PIP2
IP3
(second messenger)
DAG
Cellular response
GTP
Ca2+
(second
messenger)
IP3-gated
calcium channel

22. Calcium ions as second messengers affect pathway for heart muscle contraction. - Ca channel blockers as heart medications.

23. Step 3: Response
Cell takes action
may occur in cytoplasm or nucleus

24. Step 3: Response Nuclear Response
Signal may trigger products to be made
Pathways can regulate genes by activating transcription factors
- can turn genes
on or off
Ex: growth factor signals protein synthesis for proteins needed for growth

25. Step 3: Response Cytoplasm Response Response may regulate activities
Ex: hormone epinephrine
signals breakdown
of glycogen to
glucose
Epineprine acts thru GPCR and activates relay molecules (cAMP/RPKs) Activates enzyme to break down glycogen Pathway amplifies hormonal signal and activates many G proteins

26. Response: Cell Signaling Specificity
The type of proteins a cell has determine which signals it responds to and how it responds
ex: liver and heart cells will do different things when activated by same hormone, epinepherine
liver: increases glycogen breakdown
heart: increases heart rate

27. Response: Scaffolding Proteins
Large relay proteins to which other relay proteins are attached
Increases efficiency of signal
May directly activate other relay proteins

28. STP Problems/Defects
Examples: Diabetes Cholera Autoimmune disease Cancer Neurotoxins, poisons, pesticides Drugs (anesthetics, antihistamines, blood pressure meds)

29. Termination of the Signal
Inactivation mechanisms
Signal must be turned off so new signals can be received
Binding of signal molecules is reversible
activated receptors   inactive receptors
Response ceases once concentration of signal molecules drops below a certain threshold, not enough bound on receptor and receptor becomes inactivated

30. Apoptosis Pre-programmed cell death “cell suicide”
damaged, infected, old cells
triggered by signals that activate cascade of “suicide” proteins (caspase)
Purpose:
protects surrounding cells from digestive enzymes
Animal development and maintainence
may be involved in
diseases such as
Parkinson’s and
Alzheimer’s
and some cancers
(failure of apoptosis)

31. Response:
Example of apoptosis: Paw development in the mouse

32. Cell Signaling in Systems: Endocrine Diabetes (insulin- protein hormone)
Positive feedback Insulin released in response to rise in blood glucose Insulin binds to insulin receptor Leads to cascade of cellular responsed to increase utpake of glucose into the cells Negative feedback Insulin inhibits production and release of .glucose into the cells

33. Cell Signaling in Systems: Endocrine Testosterone (lipid hormone)

34. Cell Signaling In Systems: Immune
T-cells (type of WBC)
assist other white blood cells in immunologic processes
Interluken - 17 (Il-17) : cytokine, helps activate T cells
Many new drugs being developing that inhibit this pathway by binding with receptors and reducing production of WBC which cause attack normal body cells and cause inflammation

35. Cell Signaling In Systems: Nervous
Neurotransmitters
chemical messengers
released into synaptic cleft
cause channels to open which passes along the “message”

36. Cell Signaling: Infections
Cholera
Disease acquired by drinking contaminated water (w/human feces)
Bacteria (Vibrio cholerae) colonizes lining of small intestine and produces toxin
Toxin modifies G-protein involved in regulating salt & water secretion
G protein stuck in active form  intestinal cells secrete salts, water
Infected person develops profuse diarrhea and could die from loss of water and salts