21.10:
Cell Signaling Feedback Loops
Cells use feedback loops to sustain, amplify, and inhibit the signals generated in signaling pathways.
A positive feedback loop occurs when a downstream component in a signaling pathway activates an upstream component. The loop can lead to a sustained signaling response that continues in the absence of an extracellular signal.
The sustained signals cause further activation of multiple downstream signaling components, resulting in amplification of the signal, which may increase with time.
A negative feedback loop occurs when a downstream component in a signaling pathway inhibits an upstream component resulting in dampening or stopping the response.
Since a continuous signal can be harmful to cells, the intensity and duration of a signal are controlled by negative feedback.
Positive and negative feedback can regulate distinct cell signaling pathways or be coupled together to control the same signaling pathway.
21.10:
Cell Signaling Feedback Loops
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop stabilizes the response. For example, rapid Ca2+ uptake by the mitochondria triggers negative feedback to limit and stabilize Ca2+ concentration in the cytosol even when the signal for uptake persists.
Adaptation
Negative feedback mechanisms allow cellular systems to adapt to small changes in input signals. The adaptation can occur due to receptor inactivation, where the binding of signaling molecules can induce temporary sequestration of the receptors. For example, GPCRs involved in chemotaxis are down-regulated when not required.
Positive feedback loops
The positive feedback loop in a cell performs different functions such as signal amplification and response time modulation.
Signal amplification
Positive feedback loops amplify an initial signal in a relative or absolute manner. For example, when four molecules of IP3 bind to its receptor, the Ca2+ channel on the ER is partially activated to release Ca2+. The released Ca2+ triggers a positive feedback loop, fully activating the channel and releasing more Ca2+ ions.
Response time modulation
Positive feedback can change the response timing by accelerating or prolonging the time for the signaling system to generate a response. For example, positive feedback accelerates the response by opening IP3-gated Ca2+ ion channels, rapidly achieving a saturating concentration.