chapter 1 - Bentham Science

22 HPFP: Recent Advances in Insects and Other Arthropods Vol. 1 Van der Horst and Rodenburg
reviews, see [8, 9]). The three locust AKHs co-localize to the secretory granules [15], implying that, in
response to flight activity, all three AKHs are released simultaneously. In addition, expression of the genes
for all three AKH precursors is stimulated by flight activity, suggesting that all three AKHs are involved in
flight-related processes [7]. This hypothesis is supported for AKH-I and -III by the increased degradation of
the radiolabeled pools of these peptides in the hemolymph during flight activity compared to that in the
resting situation, whereas in contrast, half-life of the hemolymph pool of AKH-II, which is less abundant
and degraded at rest more rapidly than AKH-I, was almost similar in both physiological conditions,
suggesting its role during flight to be limited ([4]; for review, see [8]). A study in which the two AKHs
from S. gregaria (AKH-I and –II) were measured by radioimmunoassay showed the concentrations of both
AKHs to increase within 5 min after initiation of flight and to be maintained at approximately 15-fold
(AKH-I) and 6-fold (AKH-II) the resting levels over flights of at least 60 min, implying that during the
phase of flight after 5 min, the release of hormones should approximately match that of their degradation
[16]. Degradation of the (single) AKH in the hemolymph of adult females of the cricket Gryllus
bimaculatus, which do not fly well, was estimated to be remarkably short (half-life approximately 3 min) in
the resting state [17].
The amounts of AKHs released during flight represent only a minute portion of the huge stores of AKHs
harbored in the adipokinetic cells. On the other hand, newly synthesized AKH molecules were shown to be
preferentially released over older ones (last in, first out) [18, 19], suggesting that a major portion of the
stored hormones belong to a non-releasable pool of older hormone (for reviews, see [8, 9]). Both the
multifactorial control mechanism for AKH release and the strategy in hormone synthesis and storage
adopted by the locust adipokinetic cells to comply with variations in secretory demands have been studied
extensively and are detailed in several reviews [8, 20, 23].
It is interesting to note that, in addition to AKHs, also the APRPs encoded by the AKH genes are released
during flight activity and might have specific functions. In species with only one AKH gene, only an APRP
homodimer can be formed, in contrast to the homo- and heterodimers in locust species as discussed above.
Intriguingly, aligning of all known AKH preprohormone genes showed the APRP region to be better
conserved in evolution (nematodes, insects, crustaceans) than that of AKH, suggesting an important
biological role [24]. However, although APRPs have been tested extensively in a large variety of bioassays,
APRP function has not yet been uncovered [24, 25].
In a peptidomic survey of the locust neuroendocrine system, the corpora cardiaca of both L. migratoria and
S. gregaria were shown to contain the two processing products of the APRPs, AKH-JP I and II [26].
However, evidence for the release of these joining peptides is lacking so far [14]. Joining peptides (JP) have
also been reported to result from vertebrate proopiomelanocortin (POMC) processing; the lack of
phylogenetic structural conservation of JP in mammals suggested, however, that the peptide does not exert
a biological activity [27].
AKH SIGNAL TRANSDUCTION AND MOBILIZATION OF SUBSTRATES FOR FLIGHT
Binding of the AKHs to their plasma membrane receptor(s) at the insect fat body cells is the primary step to
induce the signal transduction events that ultimately lead to the activation of target key enzymes and the
mobilization of substrates for energy generation. However, in spite of many efforts, insect AKH receptors
have been identified only recently. Several lines of evidence suggested the locust AKH receptor(s) to be G
protein (Gs and Gq)-coupled (reviewed in [28, 29]); the general properties of GPCRs are remarkably well
conserved during evolution (reviewed in [30]). However, the AKH receptor(s) of L. migratoria are as yet
unidentified. The AKH receptors of the fruitfly Drosophila melanogaster and the silkworm Bombyx mori
were the first to be identified at the molecular level and shown to be GPCRs structurally related to the
mammalian gonadotropin-releasing hormone (GnRH) receptors [31]. Subsequently, an AKH receptor from
the cockroach (Periplaneta americana) was identified [32]; the production of two intrinsic AKHs in P.
americana (Periplaneta AKH-I and –II; [33, 34]) may suggest the presence of a second AKH receptor. A
similar cockroach AKH receptor was also identified by another group [35]; there are, however, differences
in one amino acid residue as well as in the response towards the two Periplaneta AKHs (cf. [32]). In the