1. Cell Communication (Signaling) Part 1
AP Biology
Cell Communication (Signaling)
Part 1

2. Important concepts from previous unit:
Chemical molecules have distinct shapes and densities based upon the number of each subatomic unit.
Cell membranes interact with the surrounding environment.
The Extra Cellular Matric (ECM) is involved in cell communication.

3. Cell – to Cell Communication
It is absolutely essential for multi-cellular organisms to survive and function properly.
Communication is accomplished mainly by chemical means.

4. Types of signaling that can occur between cell or organisms:
Direct
Involves physical contact between cells or organisms.
Could also involve passage from plant cell to another plant cell through the plasmodesmata (holes) in the cell wall of adjacent cells.

5. Plants: Plasmodesmata
Are channels that perforate plant cell walls
Interior
of cell
0.5 µm
Plasmodesmata
Plasma membranes
Cell walls
Figure 6.30

6. Types of Intercellular Junctions in animals
Tight junctions prevent
fluid from moving
across a layer of cells
Tight junction
0.5 µm
1 µm
Space
between
cells
Plasma membranes
of adjacent cells
Extracellular
matrix
Gap junction
Tight junctions
0.1 µm
Intermediate
filaments
Desmosome
Gap
junctions
At tight junctions, the membranes of
neighboring cells are very tightly pressed
against each other, bound together by
specific proteins (purple). Forming continu-
ous seals around the cells, tight junctions
prevent leakage of extracellular fluid across
A layer of epithelial cells.
Desmosomes (also called anchoring
junctions) function like rivets, fastening cells
Together into strong sheets. Intermediate
Filaments made of sturdy keratin proteins
Anchor desmosomes in the cytoplasm.
Gap junctions (also called communicating
junctions) provide cytoplasmic channels from
one cell to an adjacent cell. Gap junctions
consist of special membrane proteins that
surround a pore through which ions, sugars,
amino acids, and other small molecules may
pass. Gap junctions are necessary for commu-
nication between cells in many types of tissues,
including heart muscle and animal embryos.
TIGHT JUNCTIONS
DESMOSOMES
GAP JUNCTIONS
Figure 6.31

8. Direct Contact

9. Local
Growth factors that are released into a localized area. (Usually for normal growth or repair.)
Another example is at the synapses of neurons. (Not direct contact because of the synaptic cleft.)
Another example, a teacher speaking to a class of students.
Long Distance
Hormones (They are released in one part of the body to travel to another part of the body.)
Pheromones (Chemical mate attractants released into the environment.)

10. Local and Long Distance within an organism.

12. Phermones

13. Signal Transduction Pathway (It is analogous to talking on the phone.)
Earl Sutherland won the Nobel Prize in 1971 for this discovery. He worked at Vanderbilt University.

14. Earl Sutherland

15. Three parts to the pathway:
Reception - Molecule binding to membrane receptor protein. (It is like the phone ringing.)
I don’t know anything about the actual call. I only know the phone is ringing. I will need to change the ringing into something I can understand.

16. Step 1: Reception

17. Transduction (means “to change or carry through”) (It is like answering the phone.)
This is a series of steps in the changing of the signal to something the cell can understand at the nucleus or in the cytoplasm.
It would be this series of steps: Pick the phone up, move the phone to your mouth, say hello, and wait for the conversation to begin. Now that the conversation is occurring, I can understand what the message is that was initiated by the ringing of the phone.

18. Step 2: Transduction

19. Response - This usually involves making something or turning on/off an enzymatic process.
Usually involves DNA transcription and translation or enzymes INSIDE the cell.
Now that I know what the phone message was for; I hang up the phone and do what I was asked to do. The pathway is now complete and the action/response has occurred.

20. Step 3: Response
Ensures that crucial activities occur in the right cells, at the right time, and in proper coordination with other cells.

21. Ligand - This refers to the actual signal molecule.
The ligand binds to the receptor protein (which are like cell “hands”) on the cell membrane or inside the cell.
Think of cells like a blind, deaf, and mute individual. They could effectively still communicate and understand their environment by using their hands to touch and feel.
The attachment causes a conformational shape change in the receptor protein that sets in motion the transduction pathway.
Different ligands can initiate different response, this is important when considering chemical based medicines.

22. See the CONFORMATION SHAPE CHANGE by the receptor protein caused by the ligand binding.
Signal
molecule
(ligand)
Gate
closed
Ions
Plasma
membrane
Ligand-gated
ion channel receptor
Gate open
Cellular
response
Gate closed

24. Cell Communication (Signaling) Part 2
AP Biology
Cell Communication (Signaling)
Part 2 24

25. Important concepts from previous units:
Phosphorylation occurs by the hydrolysis of a phosphate ion from ATP and attaching it to a molecule.
Enzymes are proteins whose names usually end in “ase”.
Enzymes control cellular processes by feedback (negative or positive) mechanisms.

26. Phosphorylation and Hydrolysis26

27. The most important receptor protein pathways in cells:
G- Protein Pathway - This is the most common pathway used by cells.
G- Protein Linked Receptor
This protein serves as the attachment point for the Ligand. It is found in the plasma membrane of a cell. (This acts like the “hands” for the cell.)
It will change shape upon attachment of the proper ligand.
ALL cells possess G protein receptors. This allows them to interact with and respond to the environment around them.

28. Receptor Protein 28

29. G- Protein - This protein or enzyme acts as a relay protein carrying the message to the appropriate location.
Phosphorylation is possible due to the shape change that occurred with the receptor protein. This process will turn on the G-protein.
The activated G-protein then travels to the appropriate enzyme or protein to phosphorylate it. (It is usually GTPase.)
The GTPase will then turn on or off the necessary process in the cytoplasm or nucleus. (Mostly transcription/translation.)

30. G protein Receptor 30

31. Tyrosine- Kinase Pathway - This pathway is involved with growth/emergency repair most of the time.
It has the ability to act like a catalyst for rapidly activating several relay proteins. (6 at one time.)
This is a great example of structure = function. In repair, you need to get multiple processes going quickly to prevent possible cell or tissue death.

32. Tyrosine – Kinase Receptor32

33. Ion Channel Receptors (Such as found at synapses of neurons.)
A.K.A. Ligand-gated Ion Channels.
These act as a control of a particular signal. Like letting sodium into a post-synaptic neuron. The “gate” is opened by the attaching of the neurotransmitter (the ligand) to the receptor protein. Once the gate is opened now the charged sodium ions can enter the cell to start depolarizing that cell.

34. Ion Channel Receptors Signal molecule (ligand) Gate closed Ions Plasma
membrane
Ligand-gated
ion channel receptor
Gate open
Cellular
response
Gate closed 34

37. INTRAcellular Receptors
These receptors are mostly for receiving hormones and steroids. Since these molecules are lipids, they don’t need receptor proteins on the cell membrane. They travel into the cell by diffusing across the phospholipid bi-layer.
A.K.A. Transcription Factors – the usually start the making of mRNA within the nucleus.

38. Intracellular receptors38

39. Secondary Messengers - These are relay molecules within the cell’s cytoplasm.
Usually they are ion based molecules within a cell. These can MOVE about inside the cell.
Most common types:
Cyclic AMP (cAMP)-Made by Adenylyl Cyclase from ATP

40. First messenger
(signal molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G-protein-linked
receptor
GTP
ATP
Second
messenger
cAMP
The first messenger activates a G protein linked receptor, which activates a spefic G protein. In turn, the G protein activates adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The cAMP then activates another protein, usually protein kinase A.
Protein
kinase A
Cellular responses 40

41. Ca++ (Calmodulin) and IP3 (Inostol Triphosphate)
These are mainly involved in helping to create and control muscle contraction.
The ligand (first messenger) for a muscle contraction comes to the cell. It combines with the membrane bound receptor protein. A shape change occurs in the receptor protein. The shape change allows for the inactive G protein to attach to the receptor protein and become phosphorylated by ATP. The activated G-protein will then travel to the inactive PIP2. The g-protein will break a bond in the PIP2 to convert it to an active state molecule called IP3. The IP 3 will travel to the endoplasmic reticulum of the muscle cell. The endoplasmic reticulum is like a storage place for Calcium ions. To open the storage facility you need a key. The key here is the secondary messenger IP3. The IP3 binds to a receptor protein on the endoplasmic reticulum. This causes a shape change to occur in the receptor protein. The shape change now allows the calcium ions (in the form of Calmodulin) to come out into the cytoplasm. The calmodulin (a secondary messenger too) will go and attach to the myosin microfilaments and thereby initiate a muscle contraction using the sliding filament theory.

42. Secondary Messenger Calmodulin
EXTRACELLULAR
FLUID
Signal molecule
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
PIP2
Phospholipase C
IP3 (second
messenger)
IP3-gated
calcium channel
Cellular
re-
sponses
Various
proteins
activated
Endoplasmic
reticulum (ER)
Ca2+
Ca2+
(second
messenger)
CYTOSOL 42

44. Cell Communication (Signaling) Part 3
AP Biology
Cell Communication (Signaling)
Part 3 44

45. Important concepts from previous units:
Enzymes regulate (control) cell processes.
Phosphorylation is the binding of a phosphate to a molecule with the intent of making it “work”.
ATP is the molecule cells use for cellular “work”.

46. Cellular Response
The end product of the pathway is about the regulation of some cell process.
The responses are usually protein synthesis or product synthesis. (Turning them on/off.)

47. The Big picture Growth factor Reception Receptor Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
Response P
DNA
Gene
NUCLEUS
mRNA 47

48. Kinases “turn on” processes Phosphotases “turn off” processes48

49. Protein Kinase Cascades
KINASES turn ON processes by phosphorylating the molecule.
The point of the cascade is to amplify the signal. (It keeps cells from making excess ligand signals. We only need one molecule to activate a process in that cell.)
Each step in the cascade can amplify a signal; but it can also control the reaction rate of the process.

50. Kinases “turn on” processes Phosphotases “turn off” processes50

51. Protein Phosphotase Cascades
Turn OFF processes by removing a phosphate ion from the molecule.
Same as “B” and “C” above.

52. Small signal produces a BIG response52

53. Amplification of the Signal
Only need small amount of the ligand to convey the message. (This conserves E and materials.)
The cascades amplify the signal at each step. (1 becomes 2. 2 becomes 4. 4 becomes 8, and so forth.)
Structure = Function
Different kinds of cells have different kinds and numbers of protein receptors. Each controls a different process.

54. Scaffolding Proteins
This allows for direct contact stimulation of multiple relay proteins at one time. (Similar to a Tyrosine-Kinase receptor protein. (Can you see how the scaffolding proteins might have evolved into the “one”
half of a Tyrosine- Kinase protein over time? Then putting two next to each other over time?)

55. Scaffolding Proteins Signal Plasma molecule membrane Receptor Three
different
protein
kinases
Scaffolding
protein 55

56. Tyrosine – Kinase Receptor (Evolution – Change over TIME)56