Differences Between Transmembrane and Intracellular Receptors
- Cell signaling involves receptors that recognize signaling molecules and initiate a cellular response.
- These receptors can be classified into transmembrane receptors (in the plasma membrane) and intracellular receptors (in the cytoplasm or nucleus).
- The location and structure of these receptors determine how they interact with ligands and trigger specific pathways.
Receptor
A receptor is a protein that detects and responds to specific signals. They bind to signalling molecules(ligands) to initiate a cellular response.
Transmembrane Receptors Are Gatekeepers of the Plasma Membrane
Transmembrane receptors
Transmembrane receptors are embedded in the plasma membrane and interact with signalling molecules that cannot cross the membrane.
Structure and Distribution of Amino Acids
- Hydrophobic Core: The part of the receptor that spans the membrane contains hydrophobic amino acids, allowing it to interact with the lipid bilayer.
- Hydrophilic Regions: The regions exposed to the extracellular and intracellular environments are composed of hydrophilic amino acids, enabling interaction with aqueous solutions.
- Adenosine Receptor:
- This transmembrane receptor has seven alpha helices that traverse the membrane.
- Its ligand-binding site is exposed to the outside, allowing adenosine to bind and trigger a response inside the cell.
Interaction with Signalling Molecules
- Hydrophilic Ligands: Transmembrane receptors bind to ligands that are hydrophilic and cannot cross the lipid bilayer, such as peptides or neurotransmitters.
- Signal Transduction: Binding of the ligand induces a conformational changein the receptor, activating intracellular signalling pathways.
- G-Protein-Coupled Receptors (GPCRs)
- When a ligand binds to a GPCR, it activates a G protein, which then triggers a cascade of intracellular events, such as the production of cyclic AMP (cAMP).
Intracellular Receptors Are The Cell’s Internal Responders
Intracellular receptors
Intracellular receptors are located within the cytoplasm or nucleus and interact with signalling molecules that can cross the plasma membrane.
Structure and Distribution of Amino Acids
- Hydrophilic Surface: Intracellular receptors have hydrophilic amino acids on their surface, allowing them to remain soluble in the aqueous environment of the cytoplasm or nucleus.
- Oestradiol Receptor
- This receptor binds to the steroid hormone oestradiol in the cytoplasm.
- The hormone-receptor complex then moves to the nucleus, where it regulates gene expression.
Interaction with Signalling Molecules
- Hydrophobic Ligands: Intracellular receptors bind to ligands that are hydrophobic and can diffuse through the lipid bilayer, such as steroid hormones.
- Direct Gene Regulation: The ligand-receptor complex often acts as a transcription factor, binding to DNA and influencing gene expression.
- Testosterone
- This hormone diffuses into target cells, binds to its receptor in the cytoplasm, and the complex then enters the nucleus to activate genes involved in muscle growth and development.
Key Differences Between Transmembrane and Intracellular Receptors
| Feature | Transmembrane Receptors | Intracellular Receptors |
|---|---|---|
| Location | Embedded in the plasma membrane | Located in the cytoplasm or nucleus |
| Ligand Type | Hydrophilic (cannot cross membrane) | Hydrophobic (can cross membrane) |
| Amino Acid Distribution | Hydrophobic core; hydrophilic ends | Hydrophilic surface |
| Signal Transduction | Indirect, via secondary messengers | Direct, often regulates gene expression |
| Example | G-protein-coupled receptors (GPCRs) | Steroid hormone receptors |
Why Do These Differences Matter?
- Specificity of Response: The location and structure of receptors ensure that only specific signalling molecules can trigger a response.
- Adaptation to Ligand Properties: Transmembrane receptors are adapted to hydrophilic ligands that cannot cross the membrane, while intracellular receptors are suited for hydrophobic ligands that can diffuse through the lipid bilayer.
- Diversity of Cellular Responses: Transmembrane receptors often initiate rapid, short-term responses (e.g., ion channel opening), whereas intracellular receptors typically regulate long-term processes like gene expression.
- Remember that the distribution of hydrophilic and hydrophobic amino acids in a receptor is critical to its function and location.
- This principle also applies to other membrane proteins, such as transporters and enzymes.
- The relationship between structure and function is a recurring theme in biology. How does this principle apply to other biological molecules, such as enzymes or DNA?
- Can you think of examples where a small change in structure leads to a significant change in function?
- Why do transmembrane receptors have hydrophobic regions, while intracellular receptors do not?
- How does the ability of a signalling molecule to cross the plasma membrane determine the location of its receptor?
- Can you provide an example of a signalling molecule that interacts with each type of receptor?
- Contrast the speed and effect of signals mediated by transmembrane receptors versus intracellular receptors.


