Signal Compartmentalisation Flashcards
Q1: What is signal compartmentalisation and why is it essential in cellular signalling?
A: Signal compartmentalisation refers to the spatial and temporal control of signalling pathways within defined subcellular regions or organelles. It ensures specificity of cellular responses, prevents inappropriate cross-talk between pathways, and allows differential regulation of signals within the same cell.
Q2: Explain the role of mitochondria as a signalling hub.
A: Mitochondria integrate signals related to cellular energy status, stress, and apoptosis. They regulate calcium buffering, produce ROS as secondary messengers, and initiate apoptotic signalling via cytochrome c release. Their close association with the ER also facilitates calcium exchange.
Q3: What type of signalling is associated with the nucleus and what is its functional outcome?
A: The nucleus is involved in long-term signalling, typically mediated by transcription factors like CREB. Signals such as phosphorylation cascades or nuclear translocation events regulate gene expression, leading to altered protein synthesis and long-term cellular adaptations.
Q4: Describe the signalling roles of the Golgi apparatus.
A: The Golgi is a central hub for protein trafficking and sorting. It also acts as a scaffold for signalling complexes and regulates post-translational modifications (e.g., glycosylation) that influence protein activity, localisation, or secretion.
Q5: What role does the ER play in calcium signalling?
A: The ER serves as the primary intracellular calcium store. Upon stimulation, it releases Ca²⁺ via IP3 receptors or ryanodine receptors. This calcium release initiates downstream responses like muscle contraction, secretion, and metabolism.
Q6: Describe how integrin-mediated protein-protein signalling contributes to cellular responses.
xA: Integrins link the extracellular matrix to the cytoskeleton and recruit signalling molecules like focal adhesion kinase (FAK). This activates pathways involved in cell survival, migration, and proliferation, integrating mechanical and chemical signals.
Q7: Differentiate between global and regional cAMP signalling.
A:
Global cAMP signalling: Uniform elevation of cAMP levels, typically via Gαs-coupled receptor stimulation, leading to widespread PKA activation.
Regional cAMP signalling: Spatially restricted due to the action of AKAPs and localised phosphodiesterase (PDE) activity, allowing precise control of cAMP effects.
Q8: What is the role of A-Kinase Anchoring Proteins (AKAPs) in cAMP signalling?
A: AKAPs tether PKA to specific subcellular compartments, often near its substrates, enabling localized phosphorylation events. They also bind PDEs to degrade cAMP, fine-tuning signal strength and duration in specific cellular domains.
Q9: Compare global and local calcium signalling.
A:
Global calcium signalling involves widespread cytosolic calcium elevation, leading to broad responses like gene transcription or apoptosis.
Local calcium signalling is confined to microdomains near calcium channels (e.g., near ER or plasma membrane), enabling targeted responses like vesicle release or enzyme activation.
Q10: What are calcium oscillations and how are they interpreted by cells?
A: Calcium oscillations refer to periodic fluctuations in intracellular Ca²⁺ levels. Frequency and amplitude of these oscillations encode information, with specific patterns activating different signalling pathways (e.g., activation of CamKII is frequency-dependent).
Q11: How do calcium pumps and exchangers regulate calcium signalling?
A:
Pumps (e.g., SERCA) transport Ca²⁺ back into the ER.
Exchangers (e.g., NCX) expel Ca²⁺ out of the cell. These mechanisms restore resting calcium levels and shape the temporal aspects of calcium signals.
Q12: Why is compartmentalisation important in preventing crosstalk between signalling pathways?
A: By localising receptors, second messengers, and kinases to specific subcellular sites, cells prevent unintended activation of unrelated pathways. For instance, localized PKA activation avoids indiscriminate phosphorylation of proteins in other compartments.
Q13: How can disruption in signal compartmentalisation contribute to disease?
A: Mislocalisation of signalling proteins (e.g., AKAP mutations or defective calcium buffering in mitochondria) can lead to aberrant signal amplification, insufficient responses, or inappropriate gene activation, contributing to conditions like cardiac hypertrophy, neurodegeneration, or cancer.
