Although a majority of G protein‐coupled receptors (GPCRs) act through adenylyl cyclase, many of them (GPCR) exert their effects by activating the plasma membrane‐bound enzyme phospholipase C‐β (PLC‐β). These receptors activate the so‐called inositol phospholipid signaling pathway mainly via a G protein called Gq , which activates PLC‐β in much the same way that Gs activates adenylyl cyclase. Mentioned below are some of the steps with functional characteristics of inositol phospholipid signaling pathway, one of which is not correct. Select the INCORRECT option.
IP3 is a small lipid‐soluble molecule that binds to IP3 receptor on plasma membrane thereby increasing Ca2+ concentration in the cytosol.
Inositol Phospholipid Signaling Pathway Explained
The question asks us to identify the incorrect statement regarding the inositol phospholipid signaling pathway, which is activated by certain G protein‐coupled receptors (GPCRs) via the Gq protein and the enzyme phospholipase C‐β ($\text{PLC}\text{-}\beta$). Let's analyze each given option based on the known steps of this signaling cascade.
Analyzing Inositol Phospholipid Signaling Steps
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Option 1: $\text{PLC}\text{-}\beta$ acts on phosphatidyl inositol 4,5−biphosphate ($\text{PIP}_2$), which is present in the inner half of the plasma membrane lipid bilayer.
This statement is correct. $\text{PIP}_2$ is a minor phospholipid located specifically on the inner leaflet (cytosolic side) of the plasma membrane. This strategic location allows it to be a substrate for enzymes like $\text{PLC}\text{-}\beta$ upon signaling activation near the cell surface.
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Option 2: Activated $\text{PLC}\text{-}\beta$ cleaves the $\text{PIP}_2$ to generate two products: inositol 1,4,5−triphosphate ($\text{IP}_3$) and diacylglycerol ($\text{DAG}$).
This statement is correct. $\text{PLC}\text{-}\beta$ functions as a phosphodiesterase, hydrolyzing the phosphodiester bond in $\text{PIP}_2$. This cleavage yields two distinct second messenger molecules: $\text{IP}_3$ (inositol 1,4,5−triphosphate) and $\text{DAG}$ (diacylglycerol).
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Option 3: $\text{IP}_3$ is a small lipid−soluble molecule that binds to $\text{IP}_3$ receptor on plasma membrane thereby increasing $\text{Ca}^{2+}$ concentration in the cytosol.
This statement is incorrect. Let's break down why:
- $\text{IP}_3$ is a small, water−soluble molecule, not lipid−soluble. Its water solubility allows it to rapidly diffuse through the cytosol.
- The $\text{IP}_3$ receptors are primarily located on the membrane of the endoplasmic reticulum (ER), which serves as a major intracellular storage site for calcium ions ($\text{Ca}^{2+}$).
- When $\text{IP}_3$ binds to its receptor on the ER, it acts as a ligand−gated $\text{Ca}^{2+}$ channel, causing the release of stored $\text{Ca}^{2+}$ from the ER into the cytosol. This increases the cytosolic $\text{Ca}^{2+}$ concentration, which is a key event in many signaling pathways, but the release is from the ER, not directly from the plasma membrane by a receptor located there.
Therefore, the assertion that $\text{IP}_3$ is lipid−soluble, binds to receptors on the plasma membrane, and directly increases cytosolic $\text{Ca}^{2+}$ from outside is fundamentally wrong.
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Option 4: $\text{DAG}$ gets further cleaved to release arachidonic acid, which is used in the synthesis of eicosanoids including prostaglandins. $\text{DAG}$ also activates $\text{Ca}^{2+}$ dependent protein kinase C or $\text{PKC}$.
This statement is correct. $\text{DAG}$ remains embedded in the inner leaflet of the plasma membrane. It can be further metabolized by other enzymes. One fate is cleavage to produce arachidonic acid, a precursor for signaling lipids called eicosanoids (like prostaglandins). More importantly, $\text{DAG}$, in conjunction with elevated cytosolic $\text{Ca}^{2+}$, activates protein kinase C ($\text{PKC}$), a crucial enzyme that phosphorylates target proteins and mediates many downstream effects of this pathway.
Based on the analysis, the statement in Option 3 contains several inaccuracies regarding the properties and action of $\text{IP}_3$ in the inositol phospholipid signaling pathway.
Important Questions from Cell signaling
In the table below Column A lists ligands and Column B lists classes of receptors
Column A Column B A Serotonin i Binding activates a G-protein which activates or inhibits an enzyme that generates a specific second messenger and opens ion channel B Interferons ii Binding causes receptor monomers to dimerize. Dimeric receptor then interacts with and activates one or more cytosolic tyrosine protein kinases C Glycine iii Binding changes the conformation of the receptor so that specific ions flow through it D Insulin iv Binding leads to activation of intrinsic tyrosine kinase activity Which one is the correct match?
Receptor for which one of the following proteins spans the plasma membrane of target cells but DOES NOT contain intrinsic protein kinase activity?
Which one of the following amino acids is characteristic of and is conserved in response regulator of plant two-component systems?
Which one of the following signaling molecules is NOT a protein or a peptide?
Receptor tyrosine kinases (RTKs) form a large and important class of cell surface receptors whose ligands are soluble or membrane bound protein or peptide hormones. Which of the following statement is INCORRECT?
