Universal Signal Detection System

Ligand

A chemical messenger molecule.

Steroids, Hormones, Insulin

Receptor

A protein found in the receiving cell's membrane, cytoplasm, or nucleus.

1. Signal Production
2. Signal Transmission
3. Signal Detection
4. Signal Transduction
   • Signal triggers internal changes.
5. Cellular Response
   • Cell changes behavior.

Signal-receptor interactions are highly specific. Though there may be molecular mimicry between ligands and their receptors that may block the receptors from activating. Cells can build more receptors to work around a tolerance.

Cells build more adenosine receptors in the presence of caffeine (which block adenosine receptors; keeps you awake).

After a receptor is activated, the signal stays on until regulation - enzymes break down the receptor or transduction pathways.

Signal Production

Cells broadcast everywhere, only certain cells receive. Specificity lets each signal only reach the intended target, saves evergy.

Insulin (a ligand) circulates the bloodstream, only muscle/liver cells have insulin receptors and can respond to insulin.

Signal Transmission

Autocrine Signaling

Cell signals itself.

Target receptors are on the same cell.

Juxtacrine Signaling

Cells signal to cells they are touching.

Paracrine Signaling

Quick signaling.

Near-distance signaling.

Rapid breakdown of ligand.

Molecules only travel a short distance to reach their target.

Endocrine Signaling

Slow and widespread.

Long-distance signaling.

Molecules have to travel throughout the entire body to reach their target.

Signal Detection

(Signal Receptors)

Intracellular Receptors

• Handles small, nonpolar ligands – molecules that can cross membranes.
• These receptors are found inside cell – in the cytoplasm or cell nucleus.
• Works slowly
  • Ligand has to ender the cell to find the receptor inside.
  • Changing dna/regulating genes takes hours or days.

Called gene regulators, binds to dna and activates or represses certain genes.

Membrane Receptors

• Handles large, polar molecules that cannot cross membranes.
• Sits on the membrane.
• Works quickly
  • Easier for ligand to find the receptor.

Membrane Receptor Structure

Receptor must span through the entire membrane.

• Outside part binds to ligand.
• Interior part signals the cell to take action.

G-Protein Coupled Receptors

(GPCRs)

Fast responses, amplifies signals. These activate G-proteins that then activate enzymes. This starts the signal transduction process:

• Enzymes make second messengers (secondary molecules) that amplify the message.
• Signal is heavily amplified, creates a cascade effect, each step triggers more and more proteins/enzymes.

Triggers many molecules from few ligands. Effect may last seconds to minutes.

Epinephrine (a ligand) triggers flight or fight response. Quick signaling, lots of amplification, fast response.

Receptor Tyrosine Kinases

(RTKs)

• Long term response specialists (minutes–hours).
• Activates many different pathways/processes.
• Can change gene expression/transcription.

Insulin (a ligand) is produced after a meal to tell your cells to absorb more glucose for a few hours.

Signal Transduction

1. Amplification

   • Small signal ➤ large response.

2. Specificity

   • Different signals trigger different pathways.

3. Integration

   • Multiple pathways interact and influence each other.

   • Integration Strategies

     Signal Strength Comparison

     Strongest signal wins (amount).

     Temporal Integration

     Most recent signal prioritized.

     Pathway Convergence

     Multiple signals may affect the same target.

     Cross-Talk

     One pathway may modify another pathway.

4. Regulation

   • Turning signals off
   • Prevent runaway responses
   • Regulation Strategies
     • Turn off receptor
     • Turn off ligand
     • Break down pathways

Second Messengers

These are molecules that transmit the signal within the cell. They handle intracellular communication.

cAMP (Cyclic adenosine monophosphate) is a second messenger that transmits signals within the cell.

Transduction Regulation

After a receptor is activated, the signal stays on until regulation - enzymes break down the receptor, ligand?, or transduction pathways. Receptors can get "stuck on", even w/o ligand if was already triggered, requires regulation to turn off.

Receptor Breakdown

Active receptors keep responding until they are turned off.

Endocytosis

Cell engulfs membrane receptors.

Receptor Degradation Receptor Downregulation

Break down receptors via lysosomes.

Desensitization

Modify receptors to stop responding.

As insulin signaling continues, receptors are internalized, and stop taking in glucose until they are reactivated.

Signal Molecule Breakdown

Active signaling molecules keep triggering responses until they are turned off.

• Enzymes break down signals
• Remove phosphate groups (phosphatases)
• Destroy second messengers

Enzyme phosphodiesterase breaks down cAMP ➤ AMP. This stops the signal cascade.

Opposing Enzymes

Affects the pathways, what pathways are turned on or off.

Kinase Enzyme

Acts like an on switch.

Adds a phosphate group to a protein to activate it.

Phosphatases Enzyme

Acts like an off switch.

Removes a phosphate group from a protein to deactivate it.

Cancer is a mutation in the cellular division regulation process - the signal to proceed with cellular division is stuck on.

Signal Summary

Signal Strength

How much signal is present.

Amplification

How much the signal is boosted.

Termination

How quickly signal is turned off.

Adjusting the Signal

Adjusts based on the response to cellular needs.

• Cell builds more of fewer receptors.
• Changing enzyme levels.
• Modifying signal sensitivity.