|
Kasper Astrup Eriksen
Robustness in filter designs. Implications for
receptor internalization.
Abstract
A common signaling processing step is to filter the signal.
In biology there are amble examples where the physiological
response depends on the duration of the signal. A simple
way to obtain such a filter effect is with the help of a
delay circuitry. There are at least two principally
different ways to obtain the delay: activate an activator
or by inhibiting an inhibitor. Previously a model based on
the first option has been proposed in connection with the
early signaling events in the mammalian response to
Insulin. Here we consider the equivalent model based on the
second option. We demonstrate that although the two options
are able to obtain the exact same filter characteristics,
the robustness to external perturbations are very
different. In particular is the inhibitory version
insensitive to variations in the concentration of the
inhibitor, while the cross-over frequency in the activator
case depends linearly on the concentration of the
activator. The cross-over frequency determines the
timescale that separates the two different physiological
responses metabolic versus mitogenic. This kind of
robustness is thus very important in the design of drugs
that interfere with the signaling pathway (Insulin
sensitizers). However one can not generally conclude that
the inhibitor version is the most robust as in
transcriptional feed forward loops the activate an
activator version is the most robust. Furthermore we point
out that receptor internalization effectively implement a
robust delay circuitry, and this raises the intriguing
possibility that receptor internalization quite generally
is involved in filtering of the external signal.
LU TP 04-14
|