1. Cell Signaling
A video screencast of this presentation can be accessed at:

2. Cell Signaling/Communication
Cells must be able to communicate with adjacent cells and in some cases, with cells located in other parts of the body.
Local Signaling—Communication between adjacent cells via communicating intercellular junctions.
Materials and signals may move from cell to cell. May involve plasmodesmata (in plants) or gap junctions (in animals).
Membrane bound cell surface proteins may also directly connect one cell to another cell. This is very important in the immune process and will be explored in Session 2.
Synaptic signaling—neurotransmitters travel across a synapse, from one neuron to the next, bind to receptors, and stimulate a target cell. This will be explored in session 3.

3. Plasmodesmata--a narrow thread of cytoplasm that passes through the cell walls of adjacent plant cells and allows communication between them.

4. Gap Junction--specialized intercellular connection between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulated gate between cells.

5. Synapse--a junction between two neurons, consisting of a minute gap across which neurotransmitters acts as signals between the two neurons.

6. Cell Surface proteins connecting a macrophage to a helper T cell.

7. Long Distance Signaling
In many cases, cells communicate with other cells via signaling molecules.
These signals are released by one cell and interact with receptors on the receiving cell.
Most of these signaling molecules interact with receptors located on the surface of the receiving cell (extracellular receptors). These signals are known as ligands. They are typically composed of proteins and are too large and charged to actually cross the cell membrane.
Other signals are composed of lipids. Steroids such as estrogen and testosterone are able to cross the cell membrane and interact with intracellular receptors. This allows them to act as gene regulatory proteins. Because they can enter the cell and stimulate specific genes, these signals can often stimulate slow but sustained response.

8. Long Distance Signals
Hormones—hormones travel from an endocrine gland through the circulatory system, bind to receptors, and affect specific target cells.
Pheromones--substances secreted by one animal that cause some behavioral response in a second animal. Pheromones often deal with reproduction/attraction and are often secreted in sweat or urine.
Nervous System Signals—Electrical impulses may travel long distances through a neuron. Some human neurons can reach up to 1 meter in length.

9. Steps in the Cell Signaling Process
Reception—A chemical signal binds to a receptor on the cell surface. This often triggers a conformational change in the receptor which transmits the signal through the cell membrane and into the cytoplasm of the receiving cell.
Transduction—”key word”—The chemical signal is converted to a form that can bring about a cellular response. Think of this like translating a foreign language or like converting an electrical signal in an ipod to a meaningful sound in the ipod’s headphones. Transduction also involves spreading the signal rapidly (Amplification) throughout the entire cytoplasm of the cell. This process usually occurs in a complicated series of steps called the signal transduction pathway.
Response—Crucial cellular activities are activated or deactivated. Responses can include: turning on/off specific genes, turning on/off certain chemical reactions, stimulating the breakdown of a specific substrate, and the opening/closing of specific ion channels.

10. Step 1: Reception
Please remind students that ligands can be molecules or forms of Energy. If a molecule, molecules have distinct shapes and masses. If forms of energy, light, wave, pressure, etc.

11. Step 1: Reception
Cell signals only affect the appropriate target cells because the signals act as “ligands”. Ligands are chemicals that specifically bind with other molecules much like a substrate and an active site bond (lock and key fit). The bonding often changes the shape of the receptor (conformational change) and activates the receptor.
Most receptors are on the outside of the cell membrane (extracellular) because many signal molecules are made of proteins which are too large and/or charged to pass through the plasma membrane.
Other receptors are found inside the cell (intracellular receptors). These receptors typically interact with lipid-based hormones like the steroids.

12. Step 2: Transduction
Please stress the need for conformational shape change. This identifies if this is the target tissue or not. If no conformational shape change occurs in the receptor protein; that is not the intended target.

13. Step 2: Transduction
In most cases, transduction is a multistep process.
A benefit of this is that a small number of ligands (signals) can help to activate a large number of molecules at the end of the pathway. We can say that transduction often amplifies a chemical signal along the signal transduction pathway.
Signal transduction pathway—a series of steps in which one protein activates another until the desired response is triggered. Think of this like a chain of falling dominoes. The chain splits and the number of pathways increase throughout the process.
Remember that in most cases, the ligand (signal) never enters the cell. Its signal is transduced or converted to a response through a series of chemical steps. This often involves conformational changes in proteins brought about by phosphorylation.
Phosphorylation is the process in which a phosphate group is transferred from ATP to a protein. This provides the protein with energy and activates it. Phosphorylations are often carried out by a group of enzymes known as protein kinases.

14. Step 2: Transduction/Phosphorylation Cascade

15. Step 3: Response
Make sure students understand it is either an enzyme being turned off/on or a process, such as transcription or replication, being turned on/off.

16. Step 3: Response
A signal transduction pathway regulates one or more cellular activities.
Potential responses to cell signals include:
The opening of an ion channel
The breakdown of a substance in a cell (like glycogen).
The activation of enzymes.
The synthesis of enzymes or proteins.
The turning on/off of certain genes (gene regulation).

17. Secondary Messengers
The job of a secondary messenger is to transmit the signal from just inside the cell membrane throughout the rest of the cytoplasm.
The most important secondary messenger is cAMP (cyclic adenosine monophosphate). It is usually associated with G-linked protein receptors.
cAMP is built from ATP.
Other secondary messengers include:
Calcium ions; cGMP

18. Types of Receptors—G-protein- linked (coupled) receptors
These extracellular receptors are the largest and most diverse group of receptors found in eukaryotes. G-protein-linked receptors may bind ligands which range from odor molecules to pheromones to hormones to neurotransmitters.
Once a ligand binds to the G-protein-linked receptor, a GTP molecule is attached to the alpha subunit of the receptor. The alpha subunit then breaks free and activates a protein which will create secondary messengers like cAMP. This starts the signal transduction pathway and the amplification of the signal.
Individual G-protein-linked receptors can only activate one signal transduction pathway and thus bring about one, specific response.

19. G-Protein-Linked Receptors

20. Receptor Tyrosine Kinase
These cell surface (extracellular) receptors bind and respond to growth factors and other locally released proteins that are present at low concentrations. RTKs play important roles in the regulation of cell growth, differentiation, and survival. Insulin receptors are an example of this category of extracellular receptors.
When signaling molecules bind to RTKs, they cause neighboring RTKs to associate with each other, forming cross-linked dimers. Cross-linking activates the tyrosine kinase activity in these RTKs through phosphorylation — specifically, each RTK in the dimer phosphorylates multiple tyrosines on the other RTK. This process is called cross-phosphorylation.
This allows receptor tyrosine kinases to activate multiple signal transduction pathways at a time and stimulate multiple cellular responses.

21. Receptor Tyrosine Kinase

22. Ligand-Gated Ion Channels
Certain cells, commonly called excitable cells, are unique because of their ability to generate electrical signals. Although several types of excitable cells exist — including neurons, muscle cells, and touch receptor cells — all of them use ligand-gated ion channel receptors to convert chemical or mechanical messages into electrical signals.
Like all cells, an excitable cell maintains a different concentration of ions in its cytoplasm than exists in its extracellular environment. Together, these concentration differences create a small electrical potential across the plasma membrane. When a signal, like a neurotransmitter, binds to the ligand-gated ion channel, the channel opens (conformational change) and allows a specific ion to either enter or exit the cell. This movement of ions is responsible for the generation of the electrical signal.

23. Ligand-Gated Ion Channels

24. Secondary Messenger First messenger (signal molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G-protein-linked
receptor
GTP
ATP
Second
messenger
cAMP
Help students see the location and role
Protein
kinase A
Cellular responses

25. Secondary Messenger cAMP
Adenylyl cyclase
Phosphodiesterase
Pyrophosphate
H2O P P i
ATP
Cyclic AMP
AMP
Please help students see this is an RNA Adenine molecule that has circled up. It could also be an ATP or ADP that has lost phosphates.