The insulin receptor is activated on binding insulin molecules. This leads to the activation of the downstream PI3K pathway that triggers AKT to phosphorylate and inactivate a FOXO transcription factor. The lipid phosphatase PTEN antagonizes the PI3K pathway. A reduction of function mutation in the insulin receptor dramatically increases life span of an organism. The following statements were made regarding the mutations and their outcomes. A. A gain of function mutation in AKT makes the organism long-lived. B. A FOXO deletion mutation suppresses the long life span of the organism with a reduction of function mutation in the insulin receptor. C. A PTEN deletion mutation suppresses the long life span of the organism with a reduction of function mutation in the insulin receptor. D. A loss of function mutation in the FOXO ortholog makes the worms long-lived. Which one of the following options represents the correct combination of the statements?
B and C
Insulin Signaling Pathway and Lifespan
The question describes how the insulin signaling pathway, involving the insulin receptor (IR), PI3K, AKT, and the transcription factor FOXO, influences the lifespan of an organism. It is stated that binding of insulin to the insulin receptor activates a cascade: IR > PI3K > AKT. AKT then phosphorylates and inactivates FOXO. PTEN is a phosphatase that opposes the action of PI3K.
Crucially, the question states that a reduction of function mutation in the insulin receptor dramatically increases life span. This key piece of information tells us that *reduced* activity in this pathway leads to increased lifespan. Specifically, reduced IR activity leads to less PI3K activity, less AKT activity, and consequently, FOXO remains *active* (because it's not phosphorylated by AKT). Therefore, an active FOXO is associated with increased lifespan.
We need to analyze each statement based on this understanding: reduced pathway activity/active FOXO correlates with increased lifespan, and increased pathway activity/inactive FOXO correlates with potentially reduced lifespan (or suppression of the long-lived phenotype).
Analyzing Statement A: AKT Gain of Function Mutation
Statement A says: A gain of function mutation in AKT makes the organism long-lived.
- A gain of function in AKT means AKT is more active than normal.
- More active AKT will lead to increased phosphorylation of FOXO.
- Increased phosphorylation inactivates FOXO.
- Inactive FOXO is associated with reduced lifespan (the opposite of the long-lived state caused by reduced IR function, which results in active FOXO).
- Therefore, a gain of function mutation in AKT would likely *reduce* lifespan or at least not increase it.
Statement A is likely incorrect.
Analyzing Statement B: FOXO Deletion Mutation
Statement B says: A FOXO deletion mutation suppresses the long life span of the organism with a reduction of function mutation in the insulin receptor.
- The organism already has a reduction of function mutation in the insulin receptor, which causes a long lifespan. This long lifespan is due to reduced pathway activity leading to active FOXO.
- A FOXO deletion mutation means FOXO is completely absent or non-functional. This is equivalent to FOXO being permanently inactivated.
- If FOXO is deleted, it cannot be active, regardless of the reduced upstream signaling from the mutated insulin receptor.
- Since active FOXO is required for the increased lifespan phenotype caused by reduced IR function, deleting FOXO would eliminate this key component.
- Therefore, deleting FOXO would suppress (prevent or counteract) the long lifespan phenotype caused by the reduced insulin receptor function.
Statement B appears correct.
Analyzing Statement C: PTEN Deletion Mutation
Statement C says: A PTEN deletion mutation suppresses the long life span of the organism with a reduction of function mutation in the insulin receptor.
- PTEN is a lipid phosphatase that antagonizes the PI3K pathway. This means PTEN normally reduces the activity of the pathway downstream of PI3K.
- A PTEN deletion mutation means PTEN is absent or non-functional.
- Without functional PTEN, the inhibitory effect on PI3K is removed, leading to increased activity of the PI3K > AKT pathway.
- Increased AKT activity phosphorylates and inactivates FOXO.
- The organism has a reduction of function mutation in the insulin receptor, which promotes long lifespan by leading to active FOXO.
- If PTEN is deleted, the increased pathway activity (from unchecked PI3K/AKT) will lead to inactive FOXO, counteracting the effect of the reduced IR mutation.
- This would suppress the long lifespan phenotype resulting from the reduced insulin receptor function.
Statement C appears correct.
Analyzing Statement D: FOXO Loss of Function Mutation
Statement D says: A loss of function mutation in the FOXO ortholog makes the worms long-lived.
- A FOXO ortholog is the equivalent gene in another organism (like worms).
- A loss of function mutation in FOXO means FOXO is non-functional or inactivated.
- As established, active FOXO is associated with increased lifespan, while inactive FOXO is associated with reduced lifespan.
- Therefore, a loss of function mutation in FOXO, which results in inactive FOXO, would likely *reduce* the lifespan, not make the worms long-lived.
Statement D is incorrect.
Based on the analysis, statements B and C are correct.
Important Questions from Cellular communication
In a neuron, proteins and membranes are primarily synthesized in the cell body. These materials must be transported down the axon to the synaptic region using microtubules in an anterograde fashion. Such axonal transport is directed by
Acetylcholine is a potent neurotransmitter, which is released from the neurons. After release they diffuse across the synaptic cleft and combine with nicotinic acetylcholine receptor molecules in the membrane of the postsynaptic cell. The interaction of acetylcholine with the nicotinic acetylcholine receptor produces large transient increase in the permeability of the membrane to specialized ions resulting in signal transduction for nerve impulse. Acetylcholine receptor is a
Column X represents the type of junctions and column Y represents the proteins associated with the junctions.
Column X
Column Y
A.
Anchoring junction
i.
Claudins
B.
Occluding junction
ii.
Delta-Notch
C.
Channel-forming junction
iii.
Desmoglein
D.
Signal-relaying junction
iv.
Connexin
Which one of the following options is a correct match between terms of Columns X and Y?
Bacteria employ various mechanisms to invade or enter host cells, which are either phagocytic or non-phagocytic in nature. Given below are some of the mechanisms which are generally used for carrying out this process.
A. Some bacteria express a protein called invasin that is recognized by host-cell β1 integrins.
B. Actin polymerization along with assembly of clathrin coat results in the internalization of bacteria by zipper mechanism.
C. Some bacteria, including Salmonella enterica, use trigger mechanism to inject a set of effector molecules in the cytosol through type III secretion system.
D. Some bacteria attach to host cell surface receptors inducing local elevation of Ca2+ in cell cytosol, leading to the fusion of lysosomes with bacteria containing plasma membrane vesicles.
Which one of the following represents the combination of correct mechanisms for invading non-phagocytic cells?
In C. elegans, PAR proteins segregate at the cell cortex in the zygote to establish cell polarity. This is dependent on the regulation of the cortical actin cytoskeleton by RhoA. An investigator sought to directly inhibit actin polymerization to analyze the impact of this inhibition on PAR protein localization. Which one of the following chemicals would be the most suitable?
