week 6 Signal Integration Flashcards
Define signal integration within a cell and explain why it is necessary.
✅ Model Answer:
* Definition:
Signal integration refers to a cell’s ability to process multiple, simultaneous inputs from different signalling pathways and produce a coordinated output.
* Importance:
o Ensures appropriate, nuanced cellular responses.
o Prevents overactivation or conflicting actions.
o Essential for cells exposed to multiple hormones, neurotransmitters, and growth factors simultaneously.
Describe the integration of signals controlling acid secretion in the stomach parietal cells.
✅ Model Answer:
* Multiple inputs:
o Gastrin (from G cells) → acts on CCK receptors (GPCRs).
o Acetylcholine (from vagus nerve) → acts on muscarinic receptors.
o Histamine (from ECL cells) → acts on H2 receptors.
* Integration mechanism:
o These signals converge to regulate proton pump activity.
o Depending on the combination of signals, acid secretion is either upregulated or downregulated.
o GPCR pathways converge via intracellular second messengers (e.g., calcium, cAMP) to modulate the final output.
Explain the cross-talk between calcium and cAMP pathways in cardiac muscle contraction.
✅ Model Answer:
* Baseline:
o Cardiac contraction is initiated by calcium influx during action potentials.
* Adrenergic stimulation:
o Sympathetic input via adrenaline/noradrenaline activates β-adrenergic receptors → increases cAMP.
o cAMP activates PKA, which:
Phosphorylates L-type calcium channels (enhancing calcium influx).
Phosphorylates phospholamban to improve calcium reuptake into the sarcoplasmic reticulum.
* Result:
o Increased rate and force of contraction.
o Represents direct cross-talk between cAMP signalling and calcium handling machinery.
How does calcium-stimulated adenylyl cyclase activity demonstrate intracellular integration in neurons?
✅ Model Answer:
* Mechanism:
o Certain adenylyl cyclase isoforms (AC1, AC8) are calcium-sensitive.
o Increased intracellular calcium enhances cAMP production.
o This intersection between calcium and cAMP pathways is critical for:
Synaptic plasticity.
Long-term memory formation (hippocampus).
o Example: Knockouts of calcium-sensitive adenylyl cyclases impair learning and memory.
Describe the integration of glucose and incretin (GLP-1/GIP) signals in pancreatic beta cells.
✅ Model Answer:
* Glucose:
o Increases ATP → closes K⁺ channels → depolarization → calcium influx → insulin secretion.
* GLP-1/GIP:
o Activate GPCRs → increase intracellular cAMP.
o Alone, GLP-1/GIP have little effect, but in the presence of glucose:
Amplify insulin secretion dramatically.
o Likely involves cAMP activating PKA/Epac pathways that prime the exocytotic machinery.
* Result:
o Safe drug targets (e.g., semaglutide) because they enhance insulin secretion only when glucose is elevated.
Define intercellular signal integration and describe a general example.
✅ Model Answer:
* Definition:
Intercellular signal integration occurs when communication between multiple cells leads to a coordinated tissue response.
* Example:
o Wound healing:
ATP released from damaged cells.
ATP stimulates surrounding immune cells (e.g., macrophages) to coordinate an inflammatory response.
How do gap junctions contribute to intercellular signal integration?
✅ Model Answer:
* Structure:
Gap junctions are composed of connexin proteins forming channels between adjacent cells.
* Functions:
o Allow passage of ions (electrical coupling) and small molecules like IP₃ and calcium (chemical coupling).
o Synchronize responses across tissues (e.g., smooth muscle contraction, insulin secretion across beta cells).
o Maintain uniformity in tissue responses (e.g., coordinated beating of cardiomyocytes).
Explain electrical coupling via gap junctions in pancreatic beta cells.
✅ Model Answer:
* Mechanism:
o Beta cells are electrically coupled via connexin 36 gap junctions.
o Depolarization in one cell spreads quickly across the islet.
o Ensures synchronized insulin secretion across the whole islet.
* Result:
o Sharp, collective glucose threshold for insulin release.
o Suppresses asynchronous responses from highly sensitive or insensitive cells (peer-pressure model).
Describe how gap junctions coordinate calcium waves in airway epithelial cells.
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Describe how gap junctions coordinate calcium waves in airway epithelial cells.
✅ Model Answer:
* In airway epithelia:
o Calcium signals initiated in one cell can propagate through neighboring cells via IP₃ diffusion.
o Requires functional gap junctions.
o Important for coordinated mucociliary movement and tissue-level responses to injury.
Give an example of heterocellular communication via gap junctions.
✅ Model Answer:
* Example:
o Glial cells and neurons during neuronal axonal specification.
o Gap junction communication between glia and neurons influences neuron growth direction and axonal outgrowth.
* Importance:
o Demonstrates that gap junctions also mediate signals between different cell types, not just identical ones.
How does ATP act as an extracellular integrator in immune responses?
✅ Model Answer:
* In macrophages:
o Damaged cells release ATP into the extracellular space.
o ATP binds purinergic receptors (P2 receptors) on nearby macrophages.
o Triggers activation and enhances phagocytosis.
* Example of integration across cells responding to environmental damage.
What is signal cross-talk and why is it important for integration within a cell? Provide an example.
✅ Model Answer:
* Definition:
Signal cross-talk is when two or more signalling pathways interact within a cell, influencing each other’s activity and outcomes.
* Importance:
o Ensures that the cell produces a coordinated and appropriate response.
o Prevents conflicting outputs when multiple stimuli are present.
* Example:
o Adrenergic control of the heart:
Baseline cardiac contraction is driven by calcium influx.
Sympathetic stimulation increases cAMP via β-adrenergic receptors.
cAMP activates PKA, which enhances calcium channel activity.
Cross-talk: cAMP/PKA pathway enhances calcium signalling to increase heart rate and force of contraction.
Describe how synaptic plasticity in neurons demonstrates intracellular signal integration.
✅ Model Answer:
* Synaptic Plasticity:
o Learning and memory involve strengthening synapses (long-term potentiation, LTP).
* Mechanism:
o Calcium influx activates calcium-dependent adenylyl cyclases (AC1, AC8).
o This increases cAMP production.
o cAMP activates PKA, which phosphorylates downstream targets to enhance synaptic strength.
o Integration: Calcium and cAMP pathways converge at adenylyl cyclase.
* Evidence:
o Knockout mice lacking calcium-stimulated adenylyl cyclases have impaired memory formation.
How is insulin secretion in pancreatic beta cells an example of intracellular signal integration?
✅ Model Answer:
* Inputs:
o Glucose:
Increases ATP production.
Leads to depolarization → calcium influx → insulin secretion.
o Incretins (GLP-1, GIP):
Bind to GPCRs → raise intracellular cAMP.
* Integration:
o cAMP enhances the exocytotic machinery sensitivity to calcium.
o Massive amplification of insulin secretion only when both glucose and incretins are present.
* Key Point:
cAMP alone does little unless combined with glucose-driven calcium signalling — integration of two distinct signals.
Explain the concept of autocrine signalling as a form of signal integration within a cell.
✅ Model Answer:
* Definition:
o Autocrine signalling occurs when a cell secretes a molecule that acts back on receptors on the same cell.
* Example:
o CD8⁺ T cells release interleukin-2 (IL-2) after activation.
o IL-2 acts back on the same T cell, promoting survival, expansion, and memory formation.
* Integration:
o Combines internal signals from activation with external reinforcement via autocrine loops.
How do gap junctions facilitate integration across cells within a tissue?
✅ Model Answer:
* Structure:
Gap junctions connect adjacent cells via connexin proteins, allowing direct transfer of small molecules and ions.
* Integration Mechanism:
o Enable synchronized responses (e.g., calcium waves, electrical continuity).
o Allow entire tissues (e.g., cardiac muscle, pancreatic islets) to behave like a single unit.
* Examples:
o Electrical coupling in pancreatic beta cells for unified insulin secretion.
o Calcium wave propagation in airway epithelial cells for coordinated mucus secretion.
Describe an example where gap junctions coordinate electrical signalling across a tissue.
✅ Model Answer:
* Example:
o Cardiac muscle cells.
o Action potentials spread via gap junctions (connexins) from one cell to the next.
* Result:
o Synchronous contraction of the entire heart muscle.
o Essential for coordinated pumping of blood.
Give an example of chemical coupling via gap junctions and its functional significance.
✅ Model Answer:
* Example:
o Spread of calcium and IP₃ between airway epithelial cells.
* Mechanism:
o When one cell is stimulated, calcium and IP₃ diffuse into adjacent cells through gap junctions.
* Functional significance:
o Coordinates ciliary beating to clear mucus efficiently along the airway.
How is ATP involved in integrating responses between cells during tissue injury?
✅ Model Answer:
* Mechanism:
o Injured or stressed cells release ATP into the extracellular environment.
o ATP acts on purinergic receptors on nearby immune cells (e.g., macrophages).
o Stimulates inflammatory responses, including phagocytosis and cytokine production.
* Integration:
o ATP serves as a “danger signal” that coordinates immune responses across multiple cells around the site of injury.
Explain how glial cells use gap junctions to influence neuronal axon development.
✅ Model Answer:
* Mechanism:
o Glial cells form gap junctions with neurons.
o Exchange ions and small signalling molecules to regulate neuron outgrowth and axon pathfinding.
* Significance:
o Demonstrates that gap junction-mediated integration can occur between different cell types (not just similar cells).
