What enables cells to respond to changes in the concentration of a signaling ligand ?

In summary: So, the protein will take longer to come back to equilibrium, and this will make a bigger difference when the concentration of ligand is high.
  • #1
Ahmed Abdullah
203
3
"In chemical signaling, adaptation enables cells to respond to changes in the concentration of a signaling ligand (rather than to the absolute concentration of the ligand) over a very wide range of ligand concentrations. The general principle is one of a negative feedback that operates with a delay. A strong response modifies the machinery for making that response, such that the machinery resets itself to an off position. Owing to the delay, however, a sudden change in the stimulus is able to make itself felt strongly for a short period before the negative feedback has time to kick in." -Molecular cell biology ,bruce Albert
I don't understand this paragraph. can anyone clarify this ( best with example , even paraphrasing it may help) ... I have also searched the net, for negative feedback that operate in delay... got nothing helpful.
Any help will be highly appreciated.
 
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  • #2


There's all kinds of negative feedback with delay in biosystems. I'm not really sure of context, but this sounds like the desensitization of a ligand-gated channel. The language is kind of arbitrary, though.

Could you provide more context? (chapter topic, perhaps, what kind of material are you looking at?)
 
  • #3


Pythagorean said:
There's all kinds of negative feedback with delay in biosystems. I'm not really sure of context, but this sounds like the desensitization of a ligand-gated channel. The language is kind of arbitrary, though.

Could you provide more context? (chapter topic, perhaps, what kind of material are you looking at?)

It was trying to explain how cell respond to change in ligand concentration rather than absolute concentration, in general terms. Yap it later talks about desensitization ... but I am unsure how "negative feedback with delay" works and wondering how it helps cell to respond to change in ligand concentration.

I guessed the following may be the case, but I am not sure ... Please correct me if I am wrong.

Suppose the concentration of ligand increase from C1 to C2 , as a consequence (after some intermediate steps) the target (protein or enzyme) increase or decrease it's activity and elicit the response. After certain delay because of negative feedback, the response come to a halt. At this point the existing level of ligand concentration is unable to elicit a response.
But when ligand concentration increases still, it push the existing static state resulted from some sort of equilibrium- toward a response... but eventually the negative feedback take over and halt the response.
I also assume the negative feedback is strongly coupled with the ligand concentration... that is when ligand concentration falls it also withdraw certain extent of negative feedback inhibition.
 
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  • #4


Ok, now it sounds like you're talking about allosteric modulation, whereby the gate had a second, inhibitory binding sit for non-ligand (i.e. for allosteric modulation)

I think, if the local concentration of ligand changes, it changes the energy landscape of the protein, which changes the on-off rates of allosteric modulators.
 
  • #5


Sure, I can try to clarify this paragraph for you. Essentially, cells have the ability to respond to changes in the concentration of a signaling molecule (ligand) through a process called adaptation. This means that the cell's response is not solely based on the absolute concentration of the ligand, but rather on changes in that concentration over a wide range. This is possible because of a negative feedback loop, which is a process where a response to a stimulus leads to a decrease in that stimulus. In this case, a strong response to a change in ligand concentration will trigger a mechanism within the cell that reduces the strength of the response, essentially "resetting" itself to an "off" position. However, because of a delay in this negative feedback loop, the cell is able to experience a strong response to a sudden change in ligand concentration before the negative feedback can take effect.

To give an example, imagine a cell that responds to a hormone in the body. When the hormone binds to a receptor on the cell's surface, it triggers a cascade of events inside the cell that leads to a specific response. However, if the hormone concentration is too high, the cell may become overstimulated and this could lead to negative consequences. In order to prevent this, the cell has a mechanism in place that reduces the strength of the response, essentially "resetting" itself to an "off" position. This allows the cell to maintain a balance and not become overstimulated. However, if there is a sudden increase in hormone concentration, the cell may experience a strong response before the negative feedback can take effect, but eventually the response will be reduced to maintain balance.

I hope this helps to clarify the paragraph for you. Essentially, adaptation and negative feedback mechanisms allow cells to respond to changes in ligand concentration without becoming overstimulated or unresponsive.
 

1. How do cells detect changes in the concentration of a signaling ligand?

Cells have specialized receptors on their surface or inside the cell that bind to specific signaling ligands. When the concentration of a ligand changes, it causes a change in the conformation of the receptor, triggering a signaling cascade within the cell.

2. What is the role of signaling ligands in cellular response?

Signaling ligands act as chemical messengers that transmit information from one cell to another. They bind to specific receptors on the surface of the target cell, triggering a series of events that ultimately lead to a cellular response.

3. How do cells amplify the signal from a low concentration of a signaling ligand?

Cells have mechanisms in place to amplify the signal from a low concentration of a signaling ligand. This can include multiple receptors binding to the same ligand, as well as cascades of intracellular signaling molecules that amplify the response from the initial binding event.

4. Can cells become desensitized to a signaling ligand?

Yes, cells can become desensitized to a signaling ligand if it is continuously present at high concentrations. This can occur due to internalization of the receptor-ligand complex or downregulation of the receptor expression.

5. How do cells regulate their response to changes in the concentration of a signaling ligand?

Cells have various mechanisms to regulate their response to changes in ligand concentration. This can include feedback loops, cross-talk between different signaling pathways, and negative regulators that act to dampen the response. These mechanisms help maintain balance and prevent overstimulation of the cell.

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