4.06 Cell Signalling & Response

Figure: Different types of cell signalling (you do not need to know the names)

Definition and Importance:

• It is crucial for maintaining homeostasis and managing complex bodily functions.
• Cell Signaling is the process by which cells communicate to coordinate functions and respond to changes in the environment.

• Importance in Different Organisms:
  • Single-Celled Organisms: Use signalling primarily to move towards essential resources like nutrients, enabling survival.
  • Multicellular Organisms: Rely on more complex signalling for processes such as hormone release and nerve transmission, coordinating activities across tissues and organs.

Types of Cell Signals:

• Essential for responses like reflexes and muscle contractions.
• Chemical Signals:
  • Molecules like hormones and neurotransmitters facilitate communication.
  • These molecules bind to specific receptors on target cells to trigger a response.
• Electrical Signals:
  • Involve nerve impulses that transmit information rapidly through neurons.

Figure: Cell signalling pathway (you do not need to study it)

Adaptation and Response:

• These pathways regulate various cellular activities, helping the body maintain balance (homeostasis) and respond appropriately to internal and external cues.
• Cells detect changes in the environment and adapt by activating signalling pathways.

Stages of a Chemical Signalling Pathway

A. Intracellular Signalling

• Location: Occurs inside the cell.
• Ligand Type: Typically involves hydrophobic (lipid-soluble) ligands like steroid hormones (e.g., estrogen, testosterone, cortisol).
  • Since they are lipid-soluble, these ligands can pass directly through the cell membrane.
• Receptor Location: Ligands bind to intracellular receptors located in the cytoplasm or nucleus.
• Mechanism:
  • After passing through the cell membrane, the ligand binds to an intracellular receptor, forming a receptor-ligand complex.
  • This complex often enters the nucleus (if it’s not already there) and binds to DNA, directly influencing gene expression and protein synthesis.
  • These changes are often slow but long-lasting because they directly affect transcription and protein production.
• Example: The estrogen receptor binds estrogen within cells, leading to changes in gene expression that influence cell growth, reproductive processes, and metabolism.

B. Extracellular Signalling

• Location: Begins outside the cell.
• Ligand Type: Typically involves hydrophilic (water-soluble) ligands like peptide hormones (e.g., insulin, glucagon) and neurotransmitters.
  • These ligands are unable to pass through the lipid membrane, so they rely on receptors on the cell surface.
• Receptor Location: Ligands bind to extracellular (cell surface) receptors located on the plasma membrane.
• Mechanism:
  • When a ligand binds to a surface receptor, it triggers a signaling cascade inside the cell.
  • This often involves second messengers (like cAMP or calcium ions) or G proteins that amplify and relay the signal.
  • This signaling usually leads to rapid, short-term changes within the cell, such as enzyme activation, changes in ion channels, or alterations in cell metabolism.
• Example: Insulin binds to receptors on the cell membrane, activating pathways that help cells take up glucose quickly to regulate blood sugar levels.

B1. Ligand Secretion (Signal Generation)

• Definition: A ligand is a chemical signal released by cells in response to a specific stimulus.
• Example: For instance, when blood sugar levels drop, this low blood glucose level acts as a stimulus that prompts pancreatic cells to release glucagon.
  • Glucagon’s Role: Glucagon signals the liver to release glucose, helping to raise blood sugar back to normal.

B2. Ligand Transport

• Definition: Once secreted, ligands travel to their target cells. These target cells have receptors designed to recognize specific ligands.
• Transport Method: Ligands typically travel through the bloodstream, which allows for rapid and efficient distribution throughout the body.

B3. Ligand Binding and Receptor Activation

• Binding to Receptors: Ligands specifically bind to receptors located on the surfaces of their target cells.
  • Receptor Specificity: These receptors are structured to match the shape of particular ligands, ensuring that each receptor only responds to the right ligand.
• Receptor Activation and Transduction:
  • Once the ligand binds, the receptor changes shape, activating a signal transduction process inside the cell.
  • This process relays the message from outside the cell to the inside, preparing the cell to respond to the signal.

B4. Signal Transduction and Amplification

• G Proteins and Second Messengers:
  • Often, receptor activation involves G proteins, which are proteins on the inside of the cell membrane.
  • When the receptor is activated by the ligand, the G protein triggers the release of second messengers within the cell, such as cyclic AMP (cAMP).
  • Role of Second Messengers: These molecules spread through the cell and amplify the original signal by activating additional enzymes and proteins.
• Signalling Cascade:
  • This signal amplification leads to a signaling cascade — a chain reaction where multiple enzymes are activated in sequence.
  • This cascading effect allows a single ligand-receptor interaction to lead to a large cellular response, inducing significant metabolic or structural changes within the cell.

B5. Receptor Mechanisms in Modulating Cell Activity

• Receptors influence cellular activities in different ways depending on the type of receptor and the signaling pathways involved:
• Example: The glucagon receptor on liver cells activates enzymes involved in breaking down stored glycogen to release glucose into the bloodstream, thus increasing blood sugar levels.

Ion Channel Activation:

• Some receptors, when activated, open ion channels in the cell membrane.
• Example: Acetylcholine, a neurotransmitter, binds to receptors that open ion channels, allowing ions to flow into the cell and change the membrane potential, which is essential for nerve signaling.

Enzyme Activation:

Other receptors are directly linked to enzyme activation.

Types of Receptors and Their Roles in Signalling

1. Intracellular Ligand Binding

• Ligand Type: Lipid-soluble molecules (e.g., steroid hormones like estrogen and cortisol).
• Mechanism:
  • The ligand crosses the cell membrane and binds to an intracellular receptor in the cytoplasm or nucleus.
  • This receptor-ligand complex moves into the nucleus (if needed) and binds to specific DNA sequences, acting as a transcription factor.
  • Directly influences gene expression, promoting or inhibiting the transcription of specific genes.
• Outcome: Long-lasting effects, such as changes in protein synthesis, cell growth, differentiation, and metabolic regulation.

2. Extracellular Ligand Binding

• Outcome: Immediate effects, including changes in metabolism, cell movement, shape changes, cell division, and apoptosis.
• Ligand Type: Lipid-insoluble molecules (e.g., peptide hormones like insulin, adrenaline).
• Mechanism:
  • The ligand binds to a cell surface receptor embedded in the plasma membrane.
  • This binding initiates a signal transduction pathway involving secondary messengers or enzyme cascades inside the cell.
  • Signal transduction relays and amplifies the signal to achieve rapid, short-term cellular responses.

Summary Table