1. Cellular Communication
Biology AP Todeschini

2. Cell Signaling is Nothing New
Microbes are a window on the role of cell signaling in the evolution of life
Signals and pathways are highly conserved in evolution of life

3. How Cells Communicate-Signal Transduction
3 phases of Signal Transduction
Reception-binding of a ligand(signaling molecule)
Transduction- transmission of signal into cell
Response- cellular action

4. How Signals are Sent Local Signals
Signals can be sent to nearby cells with or without contact

5. How Signals are Sent Long Distance Signals
Hormone signaling plays an important role in the endocrine and nervous system
These signals can be slow but long lasting

6. 1. Reception
Figure 11.6 Overview of cell signaling
The binding between a signal molecule (ligand) and receptor is highly specific
A shape change in a receptor is often the initial transduction of the signal
Most signal receptors are plasma membrane proteins

7. 2. Transduction Signal transduction usually involves multiple steps
Multistep pathways can amplify a signal: A few molecules can produce a large cellular response
Multistep pathways provide more opportunities for coordination and regulation of the cellular response

8. 3. Response Results in change of cellular activities
Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus

9. Receptors in the Plasma Membrane
There are three main types of membrane receptors:
G protein-coupled receptors
Receptor tyrosine kinases
Ion channel receptors

10. G protein-coupled receptor
A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein
The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive

11. Ligand binding causes shape change of receptor binds to G Protein
Intercellular portion of receptor cannot bind to G protein
G protein activates the effector protein.
Effector Enzyme tranduces signal to cause cellular response

12. Receptor tyrosine kinases
Kinase is a protein that “phosphorylates” or adds a phosphate to another molecule.
Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines residues. They form dimers when a ligand is bound.
Remain active as long as the ligand is bound.

13. In absence of ligand receptors are separate
Binding of ligand causes dimerization
Kinase portion of receptor adds phospshates
Target proteins are activated causing response

14. ligand-gated ion channel
A receptor acts as a gate when the receptor changes shape
When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

15. ligand-gated ion channel
In absence of ligand gate is closed
Ligand binding open the channel
Release of ligand allows channel to close

16. Extracellular vs. Intracellular Receptors

17. Intracellular Receptors
These receptors are not found on the outside of the cell membrane, they are found internally.
Their ligands are typically hydrophobic lipid based compounds that can easily cross the cell membrane.
Examples of hydrophobic messengers are the steroid and thyroid hormones of animals

18. Hormone (testosterone) Plasma membrane Receptor protein DNA NUCLEUS
Fig
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
Figure 11.8 Steroid hormone interacting with an intracellular receptor
NUCLEUS
CYTOPLASM

19. Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone-
receptor
complex
DNA
Figure 11.8 Steroid hormone interacting with an intracellular receptor
NUCLEUS
CYTOPLASM

20. Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone-
receptor
complex
DNA
Figure 11.8 Steroid hormone interacting with an intracellular receptor
NUCLEUS
CYTOPLASM

21. Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone-
receptor
complex
DNA
Figure 11.8 Steroid hormone interacting with an intracellular receptor
mRNA
NUCLEUS
CYTOPLASM

22. Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone-
receptor
complex
DNA
Figure 11.8 Steroid hormone interacting with an intracellular receptor
mRNA
NUCLEUS
New protein
CYTOPLASM

23. Signal Transduction Pathways
Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated
Multistep pathways can amplify a signal: A few molecules can produce a large cellular response
At each step, the signal is transduced into a different form, usually a shape change in a protein

24. Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation
Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation
This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off

25. Transduction Second Messengers
After binding of ligand to receptor there are molecules who will tranduce the signal in the cell, directly causing a cellular response.
Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases

26. Transduction Second Messengers
Cyclic AMP (cAMP) is one of the most widely used second messengers

27. Transduction Second Messengers
Calcium ions (Ca2+) act as a second messenger in many pathways
Calcium is an important second messenger because cells can regulate its concentration

28. Transduction
Calcium Ions and Inositol Triphosphate (IP3)
Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
The formation of inositol triphosphate (IP3) leads to release of Calcium from the smooth ER

29. EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein
Fig
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
PIP2
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Figure Calcium and IP3 in signaling pathways
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL

30. EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein
Fig
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
PIP2
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Figure Calcium and IP3 in signaling pathways
Endoplasmic
reticulum (ER)
Ca2+
Ca2+
(second
messenger)
CYTOSOL

31. EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein
Fig
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
PIP2
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Figure Calcium and IP3 in signaling pathways
Endoplasmic
reticulum (ER)
Various
proteins
activated
Cellular
responses
Ca2+
Ca2+
(second
messenger)
CYTOSOL

32. Overview Multistep pathways have two important benefits:
Amplifying the signal (and thus the response)
Contributing to the specificity of the response

33. Amplification
One signaling molecule can create many times more secondary signaling creating and maintaining an intense response.
Not true for lipid based ligands that must enter the cell and/or nucleus.
-Their response is slower but can be long lasting, ex: reproductive hormones(progesterone, testosterone, estrogen)

34. An Example: Epinepherine(Adrenaline)
Released from adrenals during “flight or fight”, sympathetic response of nervous system.
The ligand can have very different responses depending on the target cell.

35. Quorum Sensing in Bacteria
Communication among microbes that alters gene expression once a certain population density is achieved.
Vibrio Fisheri are a bacteria that live symbiotically within other organisms and produce a glowing protein when their density is high enough.
Bacteria can form biofilms using quorum sensing to establish complex, stable ecosystems.

36. Apoptosis Apoptosis is programmed or controlled cell suicide
A cell is chopped and packaged into vesicles that are digested by scavenger cells
Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

37. Apoptosis Apoptosis can be triggered by:
An extracellular death-signaling ligand
DNA damage in the nucleus
Protein misfolding in the endoplasmic reticulum
Normal part of organisms development

38. Diabetes
The most common medication for type 2 diabetes is Metformin. It is a drug that activates an enzyme in your cells called AMPK. AMPK is the cell signaling pathway that makes the cell activate the GLUT-4 glucose transporter in the cell wall take up glucose for energy. AMPK is normally activated during cardiovascular exercise and it takes up glucose because it needs more for the increase metabolic activity in the muscles.  When an artificial activation of AMPK is initiated by a drug, the cells are slammed with glucose it's not using.