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IB DP Biology Study Notes

3.4.4 Receptor Types and Signal Transduction

Receptors play a paramount role in cellular communication, determining how a cell perceives and reacts to external cues. Depending on their position and function, these receptors can either be on the cell's surface or within its confines, activating distinct signal transduction pathways.

Types of Receptors

Transmembrane Receptors

Transmembrane receptors, as the name suggests, traverse the cell membrane. They act as gatekeepers, translating extracellular signals into intracellular messages.

  • Structure:
    • These are complex, integral membrane proteins spanning the entirety of the plasma membrane.
    • Comprising three significant domains:
      • Extracellular domain: Recognises and binds to the external ligand.
      • Transmembrane domain: Anchors the receptor firmly within the membrane.
      • Intracellular domain: Interacts with internal cellular machinery, transmitting signals or instigating cellular responses post ligand-binding.
  • Location: Predominantly situated on the cell surface, these receptors embed themselves within the plasma membrane's lipid bilayer.
  • Interaction with Signalling Chemicals:
    • External ligands, like certain hormones or neurotransmitters, bind specifically to the extracellular domain.
    • This binding induces a significant conformational change in the receptor, particularly activating the intracellular domain.
    • This activation may either directly influence other proteins or generate secondary messenger molecules, further propagating the signal inside the cell.
Mechanism of action of Transmembrane receptors

Image courtesy of RIT RAJARSHI

Intracellular Receptors

While transmembrane receptors act on the cell's surface, intracellular receptors operate within the cell's confines, often responding to lipophilic signalling molecules.

  • Structure:
    • Typically soluble proteins, they might be simpler in design compared to their transmembrane counterparts but are no less crucial.
    • Key domains include:
      • Ligand-binding domain: Where the signalling molecule binds.
      • DNA-binding domain: Allows the receptor to interact directly with DNA, regulating gene expression.
  • Location: Found floating within the cell, either in the cytoplasm or ensconced within the nucleus.
  • Interaction with Signalling Chemicals:
    • Lipophilic ligands, capable of diffusing across the plasma membrane, enter the cell.
    • Once inside, they seek out and bind to their specific intracellular receptors.
    • This ligand-receptor interaction often results in the receptor undergoing a conformational change.
    • Post this change, the complex frequently migrates to the nucleus where it acts as a transcription factor, binding to DNA and modulating gene expression.
Diagram showing intracellular receptors using the mechanism of steroid action as an example.

Image courtesy of PH-HY

Signal Transduction Pathways

Signal transduction is the intricate process wherein an external cue gets converted into a functional cellular response. This is never a single step but rather a cascade of events, where the initial signal undergoes amplification and fine-tuning.

Transmembrane Receptor Activation

The mechanism of action commences with the binding of an external ligand to the transmembrane receptor.

  • Ligand binding: Signalling entities, either too sizeable or too polar, find it impossible to traverse the membrane. They circumvent this limitation by binding to the extracellular domain of transmembrane receptors.
  • Conformational change: This binding isn't just ornamental. It triggers a profound structural alteration in

FAQ

Yes, a ligand can bind to different receptor types, leading to diverse cellular responses. This phenomenon, known as receptor pleiotropy, ensures that a single signalling molecule can have varied effects on different cells or even within the same cell under different conditions. For instance, epinephrine (adrenaline) can bind to both alpha and beta adrenergic receptors. While the binding to one type might lead to the constriction of blood vessels, the interaction with another type could stimulate heart rate. This multi-faceted approach allows organisms to have coordinated and multifunctional responses to specific signals.

A malfunctioning or mutated transmembrane receptor can have profound implications for cellular function. Since these receptors play a crucial role in translating extracellular signals into intracellular actions, any aberration can disrupt normal cellular communication. Dysfunctional receptors may not bind ligands correctly, might fail to undergo necessary conformational changes upon ligand binding, or could improperly interact with downstream proteins and secondary messengers. Such disruptions can lead to a range of disorders, from metabolic issues to cancers. For instance, certain cancers result from continuously activated or overexpressed receptors, leading to uncontrolled cell proliferation.

Cells employ various mechanisms to ensure that signals are not perpetually active, which could be detrimental. One common method is receptor internalisation, where receptors, after binding with their ligands, are endocytosed and degraded, reducing the cell's sensitivity to that particular ligand. Another strategy is through the action of specific phosphatases that deactivate proteins activated during the signalling cascade. Additionally, the production of inhibitory proteins that block certain steps of the pathway can also quell the signal. This ensures that cells can return to their baseline state, ready to respond to new signals when they arise.

Yes, the nature of the ligand typically determines which type of receptor it interacts with. Transmembrane receptors usually bind to ligands that are large, polar, or charged, which prevent them from diffusing freely through the lipid bilayer of the cell membrane. Examples include peptide hormones and neurotransmitters. On the other hand, intracellular receptors interact with ligands that are small, non-polar, or lipophilic, allowing them to easily cross the plasma membrane. Steroid hormones like cortisol and oestradiol are classic examples of ligands for intracellular receptors because of their ability to diffuse directly into cells.

Secondary messengers play a pivotal role in the propagation and amplification of cellular signals. Once a ligand binds to a transmembrane receptor, it may trigger the generation of these intracellular molecules. They relay the message from the receptor to other proteins inside the cell. By targeting various intracellular proteins and enzymes, secondary messengers amplify the original signal manifold. This ensures that even a small number of ligand-receptor interactions can elicit a significant cellular response. Common secondary messengers like cyclic AMP (cAMP) and inositol trisphosphate (IP3) can influence a wide range of cellular processes, from metabolism to gene expression, showcasing their versatile and integral role in cellular communication.

Practice Questions

Differentiate between transmembrane receptors and intracellular receptors in terms of their structure, location, and interaction with signalling chemicals.

Transmembrane receptors are integral membrane proteins that span the plasma membrane with parts exposed both outside and inside the cell. Their structure comprises an extracellular domain for ligand binding, a transmembrane domain for anchoring, and an intracellular domain for signal propagation. They are located on the cell surface and interact with signalling chemicals that cannot easily cross the membrane, such as large or polar molecules. On the other hand, intracellular receptors are soluble proteins found inside the cell, either in the cytoplasm or nucleus. They typically possess a ligand-binding domain and a DNA-binding domain. Intracellular receptors interact with small or non-polar signalling chemicals that can diffuse through the plasma membrane, leading to direct regulation of gene expression.

Describe how the binding of a ligand to a transmembrane receptor can initiate various signal transduction pathways within a cell.

Upon ligand binding to the extracellular domain of a transmembrane receptor, the receptor undergoes a conformational change, activating its intracellular domain. This activation can have multiple effects. It can directly activate other proteins inside the cell or lead to the generation of secondary messenger molecules, like cyclic AMP (cAMP) or inositol trisphosphate (IP3). These secondary messengers further propagate the signal by targeting various intracellular proteins, leading to a cascade effect. This amplifies the initial signal and can elicit various cellular responses. The entire process ensures that the external signal is effectively conveyed and transformed into a specific intracellular action.

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