Biology Reference
In-Depth Information
FIGURE 16.5
A positive feedback loop as a bistable switch. (A) (Left panel) Receptor tyrosine kinase (EGFR) signaling network that can induce
activation of both phospholipase C
b
(PLC
b
)-protein kinase C (PKC) pathway and the RAS-RAF-MAPK pathway. MAPK activates cytosolic phos-
pholipase A-2 (cPLA2) leading to the production of arachidonic acid (AA), which together with diacylglycerol (DAG) activates PKC to enable a positive
feedback loop. This can lead to prolonged activation of both PKC and MAPK1,2. (Right panel) Activity plots of PKC vs. MAPK show how this network
can display bistable behavior. Activation of the receptor such that initial activity of PKC and MAPK is above the intersection point (point T) will move the
system to a sustained activation state wherein both PKC and MAPK stay active even after the initial signal is withdrawn (point A). Conversely, if the initial
stimulus is below point T, the system will be decay to the basal state B as soon as the stimulus is withdrawn (adapted from
[1]
). (B) A bistable switch in the
memory circuit that controls hunger state and energy homeostasis. (Upper panel) AGRP neurons (named after the Agouti-related protein, AgRP) inhibit
POMC neurons (expressing pro-opiomelanocortin) in response to circulating hormones released in the bloodstream (e.g., ghrelin) after food deprivation.
The presence of an AMPK (5
0
AMP-activated protein kinase)-dependent positive feedback loop persistently promotes synaptic activity onto AGRP
neurons to stimulate feeding behavior until the energy balance is restored. (Lower panel) The system presents similarities to a set/reset (SR) flip-flop
memory storage circuit where two hormones ('set': ghrelin and 'reset': leptin) separately signal deficit or surfeit. The model does not have a set point, but
instead has a set range that is defined by the thresholds for activation of S and R (reprinted with permission from
[85]
).
