Biology Reference
In-Depth Information
Two papers reporting the effects of a null mutation in NOS come to differ-
ent conclusions. One paper reports that a NOS null mutation results in early
larval lethality ( Regulski, Stasiv, Tully, & Enikolopov, 2004 ), while a second
publication finds that NOS is not required for Drosophila development and
results in viable flies ( Yakubovich, Silva, & O'Farrell, 2010 ). The paper dis-
cussed here ( Caceres et al., 2011 ) finds that two nonoverlapping NOS RNAi
lines have similar phenotypes and cause lethality when expressed in the pro-
thoracic gland. These seemingly contradictory results may arise when a
tissue-specific loss-of-gene-function is more detrimental than when the
same gene is mutated in all cells of the organism, possibly due to compen-
satory mechanisms. A similar case was reported for Smad2, where two
nonoverlapping RNAi transgenes cause lethality when expressed in the pro-
thoracic gland, while the published null Smad2 mutant is viable ( Gibbens
et al., 2011 ). Future research has to address whether this phenomenon is real,
or if a more mundane explanations exist.
A knockdown of NOS in the prothoracic gland via RNAi causes animals
to remain third instars, and the inability to undergo metamorphosis is likely
caused by insufficient amounts of ecdysone. How does NO signaling affect
ecdysone synthesis? NO often exerts its function by binding to heme groups,
and Henry Krause's lab showed in 2005 ( Reinking et al., 2005 ) that the
nuclear receptor E75 contains a heme moiety that, upon binding to NO,
controls its ability to interact with DHR3. This exciting discovery was soon
followed by a series of studies on the REV-ERB proteins, the vertebrate
homologs of E75. Like E75, the REV-ERBs are transcriptional repres-
sors that regulate circadian rhythms, lipid, and glucose metabolism
( Ramakrishnan &Muscat, 2006 ). The REV-ERBs also bind heme, but un-
like E75, heme-binding is not essential for protein stability, rather, it appears
that heme binds to REV-ERBs in a reversible manner. However, the tran-
scriptional repression mediated by heme-bound REV-ERBs and RORs,
the vertebrate homolog of DHR3, is reversed by the addition of NO
( Marvin et al., 2009; Raghuram et al., 2007 ). Taken together, these studies
show that heme is structurally required for E75, and NO is a ligand for this
nuclear receptor.
During prepupal development, the expression of b ftz-f1 is controlled
by the interaction of the nuclear receptors DHR3 and E75B. In partic-
ular, DHR3 induces the b ftz-f1 gene; however, E75B blocks this induc-
tivefunctionbybindingtoDHR3onthe b ftz-f1 promoter, until the
disappearance of E75B relieves this repression ( White et al., 1997 ). Is
it possible that NO regulates
the DHR3/E75B interaction in the
Search WWH ::




Custom Search