Lecture 7- Transduction –Passing the message onGlossaryGlossary Flashcards
Learning outcomes
Secondary messengers and signal transduction
*Describe and explain the role of a second messenger, and the effects they have in the cell.
*Compare and contrast the messenger systems and their effects within thecell.
*Discuss the second messengers in context with the receptor types.
Receptor types
*Describe and explain the structure and function of the four receptortypes.
*Compare and contrast the response times between the receptor types.
Signalling Cascades
A simple signal transduction pathway involving one kinase and one target protein
Phosphorylation AND dephosphorylation are required to ensure that transduction only occurs in the presence of a stimulus
How can we ensure transmission is effective?
Ensuring effective transmission in the context of signal transduction involves several key principles and practices that enhance the efficiency and fidelity of signaling processes within cells. Here are some strategies to ensure effective transmission of signals:
- Receptor Availability and Affinity
Increase Receptor Density: Cells can upregulate the expression of receptors to ensure that more signaling molecules can bind, enhancing the sensitivity of the cell to signals.
Optimize Receptor Affinity: Modifications (like glycosylation) can increase the affinity of receptors for their ligands, promoting more effective binding and signal initiation. - Signal Amplification
Amplifying Cascades: Use of signaling cascades (e.g., phosphorylation cascades) where one activated molecule activates multiple downstream targets can significantly amplify the signal, making the process more effective.
Second Messengers: Employing second messengers (like cAMP, calcium ions, or inositol triphosphate) can rapidly propagate the signal within the cell, amplifying the initial signal received from the receptor. - Spatial Organization of Signaling Components
Localized Signaling: Compartmentalizing signaling pathways within specific cellular regions can enhance efficiency. For example, keeping signaling components close together (like in lipid rafts) reduces diffusion distances and speeds up signaling.
Scaffolding Proteins: Utilizing scaffolding proteins to bring together various signaling components ensures that they can interact effectively, reducing the likelihood of signal loss. - Temporal Control of Signaling
Feedback Mechanisms: Implement positive and negative feedback loops to fine-tune the signal and ensure appropriate responses. This allows the cell to adapt to prolonged signals or prevent overstimulation.
Transient Signaling: Signals that are quickly turned off after activation can prevent unwanted or prolonged responses. For instance, degradation of signaling molecules or receptors can terminate the signal efficiently. - Cross-talk Between Pathways
Integration of Signals: Allowing different signaling pathways to communicate can enhance the overall response of the cell. This cross-talk can fine-tune responses based on multiple signals, ensuring the cell responds appropriately to complex environments. - Efficient Ligand-Receptor Interaction
High Affinity Ligands: Using ligands that have a high affinity for their receptors can ensure that binding occurs rapidly and effectively.
Multimerization: Ligands that can bind multiple receptors simultaneously (like growth factors that can cross-link receptors) can create stronger signals. - Cellular Context and Environment
Extracellular Matrix (ECM): The ECM can influence signaling by presenting ligands in a way that promotes receptor activation, enhancing transmission effectiveness.
Cell-Cell Interactions: Direct cell-to-cell communication (e.g., via gap junctions) can facilitate the transmission of signals in multicellular environments. - Use of Inhibitors or Enhancers
Modulating Pathway Activity: Pharmacological agents can enhance or inhibit specific components of signaling pathways to ensure effective transmission or to prevent unwanted signaling.
Gene Editing: Techniques like CRISPR can be used to knock out negative regulators or enhance positive regulators of signaling pathways, improving transmission.
Conclusion
By optimizing various aspects of signal transduction, cells can ensure effective transmission of signals. These strategies involve enhancing receptor binding, amplifying signals, spatially organizing signaling components, and ensuring proper temporal control of signaling. Understanding and manipulating these factors can lead to improved therapeutic strategies in contexts such as cancer treatment, regenerative medicine, and tissue engineering.
Ensuring transmission: scaffolding
Ensuring transmission: scaffolding
1.Inactive intracellular signalling proteins bind to the scaffold protein through a specific “structural motif”. The whole complex is associated with an inactive receptor.
2.The ligand/signalling molecule causes the receptor to become activated and enables the communication of the signal from one protein to another because the proteins are in close proximity to each other
Ensuring transmission: complex formation
1.The ligand/signalling molecule causes the receptor to become activated through phosphorylation.
2.Inactive intracellular signalling proteins bind to the phosphorylated amino acids on the receptor.
3.Binding causes activation of these proteins which can now start the signalling cascade.
Ensuring transmission: docking sites
1.Membrane lipids can be used as docking sites for proteins in the cascade.
2.Upon activation of the receptor by the ligand/signal there is phosphorylation of membrane lipids (phosphoinositide).
3.These hyperphosphorylated phosphoinositide are recognised by the intracellular proteins, which are then activated by induced proximity or direct modification
Secondary Messengers
Signalling Cascades –The domino effect
Amplification of extracellular signal
Enables either
*Activation of multiple pathways to induce multiple effects simultaneously.
OR
*Convergence of multiple pathways on a single target
