How Do Cells Adapt to Changes in Signaling Ligand Concentration?

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Discussion Overview

The discussion focuses on how cells adapt to changes in signaling ligand concentration, particularly through mechanisms of negative feedback with delay. Participants explore concepts related to biosystems, ligand-gated channels, and allosteric modulation, seeking clarification and examples to better understand these processes.

Discussion Character

  • Exploratory
  • Technical explanation
  • Conceptual clarification
  • Debate/contested

Main Points Raised

  • One participant cites a definition of adaptation in chemical signaling, emphasizing the role of negative feedback that operates with a delay, but expresses confusion about the concept.
  • Another participant suggests that the discussion may relate to the desensitization of ligand-gated channels, indicating that the terminology used might be arbitrary and requests more context.
  • A participant attempts to clarify the concept of negative feedback with delay, proposing a scenario where an increase in ligand concentration leads to a response that eventually halts due to negative feedback, but acknowledges uncertainty about the mechanism.
  • Another participant introduces the idea of allosteric modulation, suggesting that changes in ligand concentration affect the energy landscape of proteins, which in turn influences the behavior of allosteric modulators.

Areas of Agreement / Disagreement

Participants express varying levels of understanding and interpretation of the concepts discussed, with no consensus reached on the specifics of negative feedback with delay or its implications for cellular responses to ligand concentration changes.

Contextual Notes

Participants note the need for additional context regarding the original material being discussed, indicating that the understanding of the concepts may depend on specific definitions and examples not provided in the initial post.

Ahmed Abdullah
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"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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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?)
 


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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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.
 

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