Question

The function of 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 \(G\) protein-coupled receptors. e. All of the above

Short answer

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

Step-by-step solution

Understand heterologous desensitization

Heterologous desensitization is a regulatory mechanism that occurs when the activation of one receptor by its ligand leads to a decreased response of another, unrelated receptor to its ligand. This happens because the two receptors share common signaling molecules or are affected by the same regulatory molecules.

Evaluate Statement A

"This process occurs when the activation of one receptor leads to an increased expression of a second receptor." This statement is incorrect because heterologous desensitization involves the decreased responsiveness of another receptor, not increased expression.

Evaluate Statement B

"This process only occurs between receptors expressed on the surfaces of adjacent cells." This statement is incorrect because heterologous desensitization can also occur between receptors on the same cell if they share common signaling molecules or regulatory components.

Evaluate Statement C

"This process cannot occur between receptors expressed on the same cell." This statement is incorrect because, as mentioned earlier, heterologous desensitization can indeed occur between receptors on the same cell.

Evaluate Statement D

"This is a process that appears to involve transphosphorylation of G protein-coupled receptors." Transphosphorylation refers to the transfer of a phosphate group from one molecule to another. In the context of GPCRs, this often occurs between kinases that regulate receptor function. This statement is true, as heterologous desensitization can involve the transphosphorylation of GPCRs by kinases, causing decreased receptor sensitivity or responsiveness.

Evaluate Statement E

"e. All of the above." As we have identified that only statement D is true, this statement is incorrect.

Choose the correct answer

Based on the evaluation of each statement, the correct answer is: d. This is a process that appears to involve transphosphorylation of G protein-coupled receptors.

Key concepts

G protein-coupled receptors

G protein-coupled receptors (GPCRs) are vital components of cellular signaling, playing a crucial role in the body's response to a wide array of stimuli such as hormones, neurotransmitters, and environmental signals.

GPCRs are embedded in the cell membrane and are characterized by their seven-transmembrane domain structure. When a ligand binds to a GPCR, it causes a conformational change in the receptor. This change is then transmitted to a G protein inside the cell, which is activated and can then interact with other intracellular signaling pathways, leading to various physiological responses.

Due to their importance in cell communication, GPCRs are heavily regulated. One form of regulation is through phosphorylation, which can modulate the receptor's activity preventing overstimulation of the cell. This balance ensures that signals are properly received and responded to, maintaining homeostasis within the organism.

Transphosphorylation of GPCRs

Transphosphorylation of GPCRs is a process where a phosphate group is transferred from one molecule, typically a kinase, to the GPCR. This post-translational modification often occurs on the intracellular domains of the receptor and can significantly affect its functioning.

Through the action of kinases, transphosphorylation can lead to a decrease in the receptor's ability to activate G proteins, thereby leading to receptor desensitization. This process is a cellular mechanism to prevent overactivation and potential damage due to prolonged exposure to stimuli.

In the context of heterologous desensitization, transphosphorylation becomes even more interesting. Unlike the self-regulatory process where a receptor becomes desensitized to its own ligand, heterologous desensitization involves one receptor affecting the responsiveness of a different receptor, often due to the shared regulatory kinases that can transphosphorylate multiple receptor types, leading to a network of modulation within the cell.

Decreased receptor responsiveness

Decreased receptor responsiveness, or desensitization, is a mechanism that prevents overstimulation of a cell's signaling pathways. It is crucial for the cell to avoid excessive responses that could be detrimental to cellular functions. Desensitization can be homologous – affecting the same type of receptors – or heterologous, which impacts different types of receptors.

In the case of heterologous desensitization, the phenomenon results not from the receptor's overactivation by its ligand but from the cross-talk between different signaling pathways in the cell. This cross-reactivity can be due to shared signaling components, such as kinases, which modify multiple receptors through phosphorylation events.

Heterologous desensitization helps maintain the balance of various physiological processes, allowing the cell to appropriately regulate sensitivity to external signals and avoid inappropriate responses. Dysregulation of this process could have significant implications, such as in the development of tolerance to drugs that target GPCRs.