1. Cell Communication per Parrott

2. Cell communication processes share common features that reflect a shared evolutionary history.
a. Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment.
b. Correct and appropriate signal transduction processes are generally under strong selective pressure.
c. In single-celled organisms, signal transduction pathways influence how the cell responds to its environment.
• Use of chemical messengers by microbes to communicate with other nearby cells and to regulate specific pathways in response to population density (quorum sensing)
• Use of pheromones to trigger reproduction and developmental pathways
• Response to external signals by bacteria that influences cell movement
d. In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a whole.
• Epinephrine stimulation of glycogen breakdown in mammals
• Temperature determination of sex in some vertebrate organisms
• DNA repair mechanisms

3. Local (Short-Distance) Signaling
Cells may communicate by direct contact
Plasmodesmata in plant cells
Gap junctions in animal cells
allow ions & currents to flow directly from cell to cell -- used in smooth muscle → synchronized contractions.
Animal cells can also use cell-cell recognition
Membrane-bound surface molecules can interact and communicate

4. Local (Short-Distance) Signaling
Messenger molecules can also be secreted by the signaling cell
Paracrine Signaling:
One cell secretes (releases) molecules that act on nearby “target” cells
Example: growth factors
Juxtacrine Signaling.
Cell surface proteins from two different cells contact -- used in immune system. Similar to basic system, but signal molecule is not secreted -- remains on cell surface.
Synaptic Signaling:
Nerve cells release chemical messengers (neurotransmitters) that stimulate the target cell

5. Gland secretes signal molecule (hormone) into blood.
Major types of secreted Signals -- classified by type of cell that makes them and/or target location.
1. Endocrine:
Signal molecule secreted by specialized cells in ductless (endocrine) gland
Gland secretes signal molecule (hormone) into blood.
Target cell is often far away. Acts long range.
Examples: Insulin, estrogen, TSH (thyroid stimulating hormone) & TH (thyroid hormone)
2. Paracrine:
Usually secreted by ordinary cells
Target cell is near by -- Receptor is on adjacent cells. Act locally.
histamines (mediate allergic reactions, responses to inflammation)
prostaglandins -- initiate uterine cramps; cause fever in response to bacterial infection.
Many growth factors (like EGF)
3. Autocrine:
Like paracrine, except receptor is on same cell. ex. = some growth factors

6. 4. Neurocrine:
Neuron secretes signal molecule.
Signal molecule acts as a neurotransmitter (NT)
NT acts on receptors on neighbor (gland, another neuron or muscle). Acts locally, like a paracrine.
Examples: norephinephrine, acetyl choline.
5. Neuroendocrine:
Neuron secretes signal molecule, as in previous case.
Signal molecule acts like a hormone (travels through blood to target).
Example: Epinephrine (adrenaline).
6. Exocrine:
Exocrine gland secretions are released by ducts to outside of body (or to inside of body cavity)*. 
Secretions on outside can carry signals → target in different individual = pheromones (detected by olfactory receptors in mammals).
Chemical Communication

7. Long-Distance Signaling
Endocrine (hormone) signaling
Specialized cells release hormone molecules, which travel (usually by diffusion through cells or through the circulatory system) to target cells elsewhere in the organism

8. Three Stages of Cell Signaling
There are 3 stages at the “receiving end” of a cellular conversation:
In reception, a chemical signal binds to a cellular protein, typically at the cell’s surface (may also bind intracellularly).
In transduction, binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway.
In response, the transduced signal triggers a specific cellular activity.

9. Stage 1: Reception
The target cell “detects” that there is a signal molecule coming from outside the cell
The signal is detected when it binds to a protein on the cell’s surface or inside the cell
The signal molecule “searches out” specific receptor proteins
The signal molecule is a ligand
It is a molecule that specifically binds to another one (think enzymes!)

10. Stage 2: Transduction
This stage converts the signal into a form that can bring about a specific cellular response
One signal-activated receptor activates another protein, which activates another molecule, etc., etc. (relays)
These act as relay molecules
Often the message is transferred using protein kinases, which transfer phosphate groups from ATP molecules to proteins

11. Stage 3: Response
The signal that was passed through the signal transduction pathway triggers a specific cellular response
Examples: enzyme action, cytoskeleton rearrangement, activation of genes, etc., etc.
Diagram example: transcription of mRNA

12. The Specificity of Cell Signaling
The particular proteins that a cell possesses determine which signal molecules it will respond to and how it will respond to them
Liver cells and heart cells, for example, do not respond in the same way to epinephrine because they have different collections of proteins

13. Signal Transduction
Reception
Transduction
Response

14. 2 Types of Signals Lipid-soluble steroids & thyroid hormones
Diffuse through plasma mem.
Enter nucleus
Form “hormone-receptor complex”
H-R complex binds as transcription factors to chromosome to activate/ inactivate gene(s)
i.e. NO
Peptides & water-soluble amines
Hormone (A) binds to receptor on cell surface
Activates G- protein
Activates adenylate cyclase
Converts ATP to cAMP
cAMP activates protein kinases, which produce final effect.

15. Types of Receptors
On Cell Surface -- for water soluble signals. Three major kinds of cell surface receptors -- 
G Protein Linked Receptors; Also called G Protein Coupled Receptors or GPCRs. (TSH  & epinephrine use these.)
Protein Kinase (usually TK) Linked Receptors. These generate cascades of modifications, but do not always use 2nd messengers.
Ion Channels. Receptor is part of an ion channel. (Neurons)
Intracellular -- for lipid soluble signals. All similar, all TF's. Receptors are transmembrane proteins with an extracellular binding domain for signal. These are sometimes called "extracellular receptors" but only ligand binding domain is extracellular, not the entire protein.
Signal Transduction Pathway Animation Transduction Pathway Epinephrine

16. Cell Signaling: Extracellular
Ligand for Cell Surface Receptor
(hydrophilic: don’t cross plasma membrane)
Ion-Channel-Linked Receptors
convert chemical to electrical signals
G-protein-linked Receptors
ligand binding  G-Protein activation by exchange bound GDP for GTP
Common structure = 7-pass membrane protein
Enzyme-Linked Receptors

17. Extracellular Signaling Molecules
Many are Molecular Switches
switched on by signaling molecule, must also be turned off
Most common switching mechanisms (nicotine, morphine & heroin)
phosphorylation
signal activated kinase; (kinase = enzyme that phosphorylates a protein)
dephosphorylation – phosphatase
GTP binding proteins:
GDP bound = inactive,
GTP bound = active

18. G-Protein Linked Receptors
Some activate membrane-bound enzymes => increase “2nd messengers”
Small and water soluble and easily diffuse
2nd messenger = cAMP
adenyl cyclase => ATP to cAMP
cAMP phosphodiesterase => cAMP to ATP
cAMP dependent protein kinase activation by Camp
cAMP => both rapid and slow responses
2nd messengers = IP3 & DAG
phospholipase c => IP3 & DAG
IP3 => opens ER Ca+2 channels . >>>> cytoplasmic Ca+2.
> free Ca+2 => many effects
DAG (w free Ca+2) => activated PKC to inner face of membrane
activated PKC => many effects
2nd messenger = Ca+2
free Ca+2 => many effect via Ca+2 binding proteins
e.g. calmodulin & calmodulin dependent protein kinases

19. The G protein acts as an on-off switch.
If GDP is bound, the G protein is inactive.
If GTP is bound, the G protein is active.

20. Some regulate ion channels. Some activate membrane-bound
Some regulate ion channels Some activate membrane-bound enzymes  increase “2nd messengers”
16_19_open_K_chan.jpg

21. 2nd messengers = IP3 & DAG 2nd messenger = cAMP
16_24_cAMP_activate.jpg

22. 16_23_slowly_rapidly.jpg
Copyright © 2005 Pearson Prentice Hall, Inc.

25. Cell Signaling: Intracellular
Signaling Pathways:
Same receptor molecule can interact w/many intracellular relay systems so same signal & same receptor  different effects in different cells
Same relay system many act on many different intracellular targets

26. Signaling Cascade Critical Functions Transduce Signal
Relay signal from point of reception to point of response production
Amplify signaling molecules are found in such [low] that the effect would be minimal w/o amplification
Distribute signal to >1 process simultaneously
Modulate signal to fit other internal & external conditions
16_08_cascades.jpg

27. Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.
a. Cells communicate by cell-to-cell contact.
• Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells and killer T-cells.
• Plasmodesmata between plant cells that allow material to be transported from cell to cell.
b. Cells communicate over short distances by using local regulators that target cells in the vicinity of the emitting cell.
• Neurotransmitters
• Plant immune response
• Quorum sensing in bacteria
• Morphogens in embryonic development
c. Signals released by one cell type can travel long distances to target cells of another cell type.
1. Endocrine signals are produced by endocrine cells that release signaling molecules, which are specific and can travel long distances through the blood to reach all parts of the body.
Insulin
Human growth hormone
Thyroid hormones
Testosterone
Estrogen

28. Cell Signaling SIGNALING PATHWAYS CAN BE HIGHLY INTERCONNECTED F16-38
(like nerve networks in brain or microprocessors in a computer)
“... a major challenge to figure out how cell communication pieces fit together
to allow cells to integrate environmental signals and to respond appropriately”

29. Death Signaling, 2, 3
16_38_Signal_pathways.jpg

31. Cell Signaling in Plants
Signaling Between Plants & Pathogens
Phytochrome signaling

32. Resources Pathophysiology of the Endocrine System
Signal Transduction Pathways
Cell-Cell Adhesion in Leukocyte Extravasation
Fight or Flight Response
Fibroblast Cell Signals
Fight or Flight 2
Cell Signaling Links
Bozeman Signal Transduction Pathways
Signal Transduction by Extracellular Receptors Tutorial
Cell Signaling Flash Movies
p53 Song
Apoptosis Animation

33. Essential knowledge 3.D.1: Cell communication processes share common features that reflect a shared evolutionary history.
a. Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment. [See also 1.B.1]
b. Correct and appropriate signal transduction processes are generally under strong selective pressure.
c. In single-celled organisms, signal transduction pathways influence how the cell responds to its environment.
• chemical messengers by microbes to communicate with nearby cells and regulate specific pathways in response to population density (quorum sensing), pheromones to trigger reproduction & developmental pathways, Response to external signals by bacteria that influences cell movement
d. In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a whole.
LO 3.31 The student is able to describe basic chemical processes for cell communication shared across evolutionary lines of descent. [See SP 7.2]
LO 3.32 The student is able to generate scientific questions involving cell communication as it relates to the process of evolution. [See SP 3.1]
LO 3.33 The student is able to use representation(s) and appropriate models to describe features of a cell signaling pathway. [See SP 1.4]
Essential knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.
a. Cells communicate by cell-to-cell contact.
• Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells and killer T-cells. [See also 2.D.4]
• Plasmodesmata between plant cells that allow material to be transported from cell to cell.
b. Cells communicate over short distances by using local regulators that target cells in the vicinity of the emitting cell.
• Neurotransmitters • Plant immune response • Quorum sensing in bacteria • Morphogens in embryonic development
Essential knowledge 3.D.3: Signal transduction pathways link signal reception with cellular response.
a. Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein.
1. Different receptors recognize different chemical messengers, which can be peptides, small chemicals or proteins, in a specific one-to-one relationship.
2. A receptor protein recognizes signal molecules, causing the receptor protein’s shape to change, which initiates transduction of the signal.
• G-protein linked receptors • Ligand-gated ion channels • Receptor tyrosine kinases
b. Signal transduction is the process by which a signal is converted to a cellular response.
1. Signaling cascades relay signals from receptors to cell targets, often amplifying the incoming signals, with the result of appropriate responses by the cell.
2. Second messengers are often essential to the function of the cascade.
• Ligand-gated ion channels • Second messengers, such as cyclic GMP, cyclic AMP calcium ions (Ca2+), and inositol triphosphate (IP3)
3. Many signal transduction pathways include:
i. Protein modifications (an illustrative example could be how methylation changes the signaling process)
ii. Phosphorylation cascades in which a series of protein kinases add a phosphate group to the next protein in the cascade sequence
LO 3.36 The student is able to describe a model that expresses the key elements of signal transduction pathways by which a signal is converted to a cellular response.
Essential knowledge 3.D.4: Changes in signal transduction pathways can alter cellular response.
a. Conditions where signal transduction is blocked or defective can be deleterious, preventative or prophylactic.
• Diabetes, heart disease, neurological disease, autoimmune disease, cancer, cholera
• Effects of neurotoxins, poisons, pesticides
• Drugs (Hypertensives, Anesthetics, Antihistamines and Birth Control Drugs)