Cell Communication and Signaling

Growth vs. Cell Death

• Balance: Maintained between cell division and apoptosis.
  • Cell division promotes growth.
  • Apoptosis eliminates unwanted cells.

Types of Cell Death

1. Apoptosis:

   • A triggered, programmed process.
   • Involves internal fragmentation of cell parts.
   • A clean process where white blood cells engulf and remove the fragmented components.

2. Necrosis:

   • Cell death due to injury.
   • Cell material is released, damaging surrounding cells.

Regulation of Apoptosis

• Involves signal molecules and a family of proteins (Bcl-2 family).
  • Bcl-2 protein: Inhibits apoptosis.
  • Bak and Bax: Stimulate apoptosis if present.

Triggering Apoptosis

1. Bak or Bax Increase:
   • More Bak or Bax proteins are present.
2. Insertion into Mitochondrial Membrane:
   • Bak or Bax gets inserted into the mitochondrial membrane.
3. Cytochrome C Leakage:
   • Cytochrome C leaks out of the mitochondria.
4. Activation of Caspases:
   • Leaked Cytochrome C leads to the activation of caspases.
   • More caspases are activated, amplifying the signal.
5. Breakdown:
   • Caspases lead to the breakdown of the cytoskeleton, DNA, and nuclear envelope, resulting in fragmentation.

Cell Communication in Animals

• Types of Cell Communication Over Distance:
  • Release of hormones.
  • Circulatory system transports hormones (long-distance).
  • Example: Hormones travel long distances.
• Local Mediators:
  • Growth factors.
• Neuronal Signaling:
  • A signal diffuses a very short distance.
  • Neurons release signals called neurotransmitters.
  • Neurotransmitters interact with synapses on target cells.

Basic Components in Cell Communication

1. Signaling Cell:
   • Produces and releases a signal.
2. Signal Molecules:
   • Various types, including proteins, short peptides, gas molecules, steroids, etc.
3. Target Cell:
   • Receives the signal.
   • Needs receptors to bind to the signal.
4. Receptor:
   • A protein that can bind to signals so that the target cell can respond.

Basic Steps of Cell Communication

1. Reception:
   • A signal molecule interacts with a specific receptor at a target cell.
   • Change in shape of receptor which will activate another protein.
   • EXAMPLE: Activation of another protein.
2. Transduction:
   • Additional proteins and other molecules are activated to continue the signal internally.
   • Amplifies and relays the message.
   • EXAMPLE: Release of ions
3. Response:
   • The cell responds to the signal.

Types of Responses

• Metabolism/chemical reactions.
• Altering gene expression.
• Changes to the cytoskeleton.
• Changes in cell shape.

Types of Receptors

1. Cell Surface Receptors:

   • Embedded in the plasma membrane.
   • For large, polar, or charged molecules that cannot cross the membrane.

2. Intracellular Receptors:

   • Bind to signals that can cross the cell membrane, such as small, hydrophobic, and uncharged molecules.

Known Cell Communication Pathways That Are Intracellular

• Nitric Oxide (NO) Pathway:
  • The nervous system stimulates endothelial cells.
  • Helps regulate blood pressure.
    • If you have high blood pressure, your neuron system senses it, which leads to endothelial cells in the blood vessel to release nitric oxide.
  • Nitric oxide then diffuses into surrounding smooth muscles.
  • Tells the smooth muscle cells to relax.
  • Vasodilation: Blood pressure goes down.
  • NO diffuses into intracellular receptors.
  • Guanylyl cyclase enzyme is activated, which converts GTP to cGMP, preventing the breakdown of cGMP which raises blood flow.
• Steroid/Thyroid Hormone Pathways:
  • Hormone diffuses into cells.
  • Binds to intracellular receptors, forming a complex.
  • Complex acts as a transcription factor.
  • Leads to changes in gene expression.

Known Pathways That Involve Cell Surface Receptors

1. Ion Channel-Linked Receptors
2. G Protein-Coupled Receptors (GPCRs)
3. Enzyme-Linked Receptors

1. Example of Ion Channel-Linked Receptor

• Acetylcholine receptor.
• When acetylcholine binds to the acetylcholine receptor, it opens the channel.
• Na^+ flows through, which is involved in skeletal muscle contraction.

2. G Protein-Coupled Receptors (GPCRs)

• Receptor known as 7-pass transmembrane receptor.
• When activated, it interacts and activates a nearby G protein.
• How to turn off this pathway:
  • The G protein breaks down GTP and becomes GDP, then they come back together and turns the pathway off.

Targets of the Active Alpha Subunit

• Adenylyl cyclase.
  • Adenylyl cyclase converts ATP to cAMP, which leads to changes in gene expression.
• Phospholipase C.
  • Phospholipase C cleaves inositol phospholipid.
  • PIP2 is cleaved into DAG and IP3.

Enzyme-Linked Receptors

• Cell surface receptors.
• Types:
  • Receptor tyrosine kinase pathway (RTK).
  • JAK-STAT pathway.

Examples

1. Receptor Tyrosine Kinase (RTK) Pathway:

   • Pathway triggers cell growth/development.

2. JAK-STAT Pathway:

   • Involved in the immune response to viral infections.
   • Phosphorylation.
   • Impacts gene expression.

Summary

• Different combinations of signals can lead to different pathways being turned on.
• Combined turned on leads to different results.
• Signal turned on decrease are important in cell communication.
• Turned on changes that turn pathways off.

Group Activity: Cell Communication

Question 1: Viagra and Cell Communication

• Which cell communication pathway does Viagra affect? How does this drug influence this pathway?
  • Viagra affects the “NO” (nitric oxide) pathway.
  • It prevents the breakdown of cGMP, which raises blood flow.

Question 2: Starfish Cell Communication

• A researcher is studying cell communication in starfish. The researcher isolated a signal molecule that starfish release and then tested the response of this signal molecule in cultured starfish cells. When internal molecules were analyzed by the scientist after exposure of the starfish to the signal, cAMP levels appear to increase. Describe the cell communication pathway that could be activated by this signal molecule that would lead to increased levels of cAMP.
  • The adenylyl cyclase pathway could be activated.
  • Starting off with the activation of GPCR, then alpha/beta/gamma subunits are activated.
  • Subunits split into two, and the GTP + alpha complex activates the adenylyl cyclase, which leads to an increase of cAMP.