Question

The function of \(\mathrm{G}\) protein-coupled receptors, such as the opioid and cannabinoid receptors, can be regulated by the process of heterologous desensitization. Which of the following statements is true about this regulatory mechanism? a. This process occurs when the activation of one receptor leads to an increased expression of a second receptor. b. This process only occurs between receptors expressed on the surfaces of adjacent cells. c. This process cannot occur between receptors expressed on the same cell. d. This is a process that appears to involve transphophorylation of \(\mathrm{G}\) protein-coupled receptors. e. All of the above

Short answer

Answer: Heterologous desensitization of G protein-coupled receptors is a process that appears to involve transphosphorylation of the receptors.

Step-by-step solution

a. Activation of one receptor increases expression of a second receptor.

Heterologous desensitization is a process in which the phosphorylation of one GPCR results in the reduced responsiveness of other GPCRs that can recognize the same G-protein. This statement implies an increase in the expression of a second receptor upon activation of the first receptor, which is not true for heterologous desensitization. The correct answer does not describe the process accurately. #Step 2: Evaluate statement b.#

b. Heterologous desensitization only occurs between receptors on adjacent cells' surfaces.

This statement is also incorrect, as heterologous desensitization can occur within the same cell. It doesn't necessarily require the involvement of adjacent cells' surfaces, as it is a regulatory mechanism that occurs at the level of a single cell. #Step 3: Evaluate statement c.#

c. The process cannot occur between receptors on the same cell.

Contrary to this statement, heterologous desensitization is a process that occurs within the same cell. As mentioned before, it is a regulatory mechanism in which the phosphorylation of one GPCR reduces the responsiveness of other related GPCRs within that cell. Thus, this statement is incorrect. #Step 4: Evaluate statement d.#

d. Transphosphorylation is involved in GPCR heterologous desensitization.

This statement is true. Heterologous desensitization is a process that involves the transphosphorylation of G protein-coupled receptors by kinases, particularly GPCR kinases (GRKs) and second messenger-dependent kinases. These kinases phosphorylate specific serine or threonine residues in the receptor, which leads to the receptor's reduced responsiveness to its agonist. Therefore, option (d) is the correct answer. #Step 5: Evaluate statement e.#

e. All of the above

Since statements a, b, and c are incorrect, the correct answer cannot be "All of the above." We already identified the correct statement as option d. #Conclusion# The correct answer is option (d): Heterologous desensitization of G protein-coupled receptors is a process that appears to involve transphosphorylation of the receptors.

Key concepts

heterologous desensitization

Heterologous desensitization is a fascinating mechanism that helps regulate the activity of G protein-coupled receptors (GPCRs). Through this process, the response of a receptor becomes less responsive, not simply due to its direct activation, but because of the influence from the signaling activation of another receptor. This means that when one receptor is activated, it can cause other different receptors in the same cell to dampen their responses.
This regulatory mechanism does not depend on an increase in the expression levels of receptors. Instead, it occurs via the modification of existing receptors. It's also a process that takes place within the same cell, not necessarily requiring the receptors on the surfaces of adjacent cells. Hence, contrary to some misconceptions, heterologous desensitization is much about internal cellular communication and adaptation.

• Allows cells to adjust to varying signals quickly.
• Involves reduced receptor responsiveness through phosphorylation changes.
• Ensures balance in signaling pathways by preventing overstimulation.

transphosphorylation

Transphosphorylation is an essential biochemical process within the cell, particularly noticeable in heterologous desensitization of GPCRs. In this context, transphosphorylation refers to the transfer of a phosphate group from one receptor to another, changing their activity state. This phosphate transfer is crucial because it partly dictates how responsive a receptor will be to incoming signals.
Transphosphorylation typically happens through the action of specific kinases, especially when one receptor influences another's phosphorylation status. This phosphorylation alters the receptor's conformation, usually lowering its activity or shutting down its signaling pathway. One can think of transphosphorylation as a communication method between receptors, ensuring that no single receptor type overwhelms the cell with excessive signaling.

• Enables cross-talk between different receptor types.
• Requires kinase activity for phosphate transfer.
• Regulates receptor activity to maintain cell function.

GPCR kinases

GPCR kinases, often abbreviated as GRKs, play a pivotal role in managing receptor activity in the process of heterologous desensitization. These are specialized enzymes that phosphorylate activated GPCRs, marking them for deactivation or dampened response. They attach phosphate groups to serine or threonine residues on the receptor.
Each kinase can have specific preferences for which receptor it targets. These kinases are like the arbiters of receptor activity, providing checks and balances by ensuring that receptor signaling doesn't go unchecked. By modifying the receptors, GPCR kinases effectively turn down the signaling volume, preparing cells to receive new signals without being overwhelmed.

• Phosphorylates specific amino acids on GPCRs.
• Essential for receptor regulation and signal modulation.
• Helps maintain cellular response precision against various signals.

phosphorylation

Phosphorylation is a biochemical process that plays a central role in regulating the actions of proteins, including GPCRs. In this process, a phosphate group is added to a protein, often causing a functional change in the protein. For GPCRs, phosphorylation by kinases is fundamental to heterologous desensitization.
When GPCRs are phosphorylated, their ability to interact with G proteins may be reduced. This change often renders the receptor less sensitive to its activating signal, resetting the cell's signaling readiness. Phosphorylation is a reversible modification, which means that it can be reversed when the signal needs to be reactivated. Understanding this cycle is crucial for comprehending how cells maintain balance in their responses to a multitude of signals.

• Modifies receptor activity state by adding phosphate groups.
• Can decrease receptor sensitivity to stimuli.
• Reversible process, allowing dynamic signal regulation.