Biology Reference
In-Depth Information
In addition to activating the MAPK pathway, studies in lepidopterans
have shown that PTTH also activates a complex network of pathways that
include PKA/cAMP, calcium and PKC (
Rybczynski, 2005; Rybczynski &
Gilbert, 2006
). Whether Torso is required for activation of these alternative
pathways and whether their activation is conserved in
Drosophila
and how
they contribute to either the production and/or release of ecdysone from
the PG requires additional study.
The finding that under low nutrient conditions TOR informs the PG to
extend the growth period (
Layalle et al., 2008
) is difficult to reconcile with
the fact that starvation after critical weight accelerates metamorphosis in
Drosophila
(
Mirth & Riddiford, 2007; Stieper et al., 2008
). One explanation
might be a cross talk between the PTTH and the TOR pathway in the PG.
Previous work has shown that rapamycin inhibits PTTH-stimulated
ecdysone synthesis (
Rybczynski, 2005
). Indeed, PTTH has been shown
to regulate 4E-BP and S6 kinase (S6K), a major target of TOR (
Gu,
Yeh, Young, Lin, & Li, 2012; Rybczynski, 2005
). In addition to its stimu-
latory effect on ecdysone synthesis, PTTH has a non-steroidogenic trophic
effect on PG growth and protein synthesis (
Rybczynski, 2005; Rybczynski &
Gilbert, 1994
) and lack of PTTH reduces PG cell size (
Ghosh, McBrayer, &
O'Connor, 2010
). PTTH-induced TOR signaling seems to rely on PI3K
(
Gu et al., 2012
), suggesting that PTTH and insulin converge on PI3K to reg-
ulate PG cell growth and ecdysone biosynthesis. On the other hand, insulin
stimulation of ecdysone synthesis may, at least in part, involve cross talk with
the MAPK (
Rewitz, Yamanaka, et al. 2009
).
How do PTTH and insulin increase activity of the ecdysone biosynthetic
pathway? PTTH-stimulated ecdysone synthesis occurs within minutes and
requires translation and likely posttranslational protein modifications
(
Rewitz, Larsen, et al., 2009; Rybczynski, 2005
). The rapid increase in
the flux through the biosynthetic pathway that converts cholesterol to
ecdysone possibly involves regulation of a rate-limiting molecule(s) that acts
in, the so-called Black Box reaction(s), an early step in the biosynthetic path-
way which is not completely understood (
Gilbert et al., 2002
). Consistent
with this view, in lepidopterans PTTH stimulates the rapid increase in trans-
lation and phosphorylation of Spook, a cytochrome P450 enzyme involved
in the Black Box (
Ono, Morita, Asakura, &Nishida, 2012; Ono et al., 2006;
Rewitz, Larsen, et al., 2009
). However, it is not clear if the Black Box is the
rate-limiting reaction in all insects.
In addition to the acute regulation, PTTH elicits a long-term transcrip-
tional effect that involves upregulation of the Halloween genes encoding the
