Biology Reference
In-Depth Information
Imp-L2, expression of dALS is nutrient-dependent, however, its expression is
suppressed when amino acid restriction is induced genetically in the fat body
(
Colombani et al., 2003
). During conditions with restricted nutrients, loss of
dALS
further reduces the body size suggesting that dALS is required for
adjusting insulin signaling under nutritional stress (
Arquier et al., 2008
).
The physiological function of dALSmay therefore be to reduce systemic insu-
lin signaling under conditions where dietary protein is limiting for growth.
Manipulating dALS expression affects the larval growth rate, but not devel-
opmental timing (
Arquier et al., 2008
).
Recently a new key player in the regulation of circulating DILPs activity
was discovered, a secreted protein with similarity to the extracellular domain
of InR named
secreted decoy receptor
(SDR;
Okamoto et al., 2013
). Like Imp-
L2 and dALS, SDR is a negative regulator that functions by forming a com-
plex with circulating DILPs to antagonize their activity during development.
Larvae with loss of
SDR
have increased growth rate and final size, while
overexpression of
SDR
results in animals with a reduced size. This shows that
SDR affects physiological functions by limiting insulin-mediated growth.
Although
SDR
is expressed in various tissues including the midgut and
the imaginal discs, its non-autonomous effect on growth is a result of glia
cell-derived expression that regulates insulin signaling at the systemic level.
Expression levels of the prominent
DILPs
are unaffected by
SDR
loss of
function, supporting the idea that SDR modulates insulin signaling in the
hemolymph downstream of secretion. Like Imp-L2, SDR has the ability
to bind with DILPs but possibly independent of Imp-L2 and dALS. It is
interesting to note that SDR and Imp-L2 exhibit differential affinities for dif-
ferent DILPs.
Nutrients have opposing effect on the expression of the different factors
regulating circulating DILP activity. While Imp-L2 levels are increased in fat
body during starvation, dALS expression is decreased under such conditions
(
Colombani et al., 2003; Geminard et al., 2009; Honegger et al., 2008;
Slaidina et al., 2009
). In contrast to these more dynamic regulators, expres-
sion of
SDR
and its secretion into the hemolymph is nutrient independent
(
Okamoto et al., 2013
). Indeed,
SDR
mutants have increased body size inde-
pendent of nutrient supply. However, animals lacking
SDR
have increased
lethality under nutrient restrictions, suggesting that SDR is required to limit
insulin-mediated growth in such conditions. The difference in the action of
SDR, Imp-L2 and dALS may reflect a robustness of the system that is impor-
tant under fluctuating nutrient conditions to fine-tuning the activity of the
ligands in circulation. This may also be important for downstream responses
that have been shown to selectively decode sustained or pulse-like insulin
