chapter 1 - Bentham Science

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Adipokinetic Hormones and Their Role in Lipid HPFP: Recent Advances in Insects and Other Arthropods Vol. 1 21 long) peptides; different bioanalogues of this family have been identified in representative species of most insect orders (for reviews, see [1-3]). Despite their hydrophobic character, AKHs appear to be transported in the hemolymph in their free form and not associated with a carrier protein [4]. Although many insects possess a single AKH species, in the migratory locust, Locusta migratoria, an internationally recognized model insect for long-distance flight, a decapeptide AKH-I is present in addition to two octapeptides (AKH-II and -III). Locust AKH-I, which is by far the most abundant [5], represents the first insect neurohormone that was purified and fully characterized [6]. Details on AKH biosynthesis in insects are particularly confined to a few locust species. All three AKHs of L. migratoria are synthesized as preprohormones in the corpus cardiacum, a neuroendocrine gland located caudal to the insect brain and physiologically equivalent to the pituitary of mammals. The amino acid sequences of these prepro-AKHs, deduced from their cDNA sequences, contain a 22-amino-acid signal peptide, one single copy of AKH, a GKR or GRR processing site, and an AKH-associated peptide (AAP) [7] (Fig. 1). In situ hybridization showed the mRNA signals encoding the three different AKH precursors to be co-localized in cell bodies of the glandular lobes of the corpus cardiacum ([7], for reviews, see [8, 9]). The processing of the preprohormones of AKH-I and -II has been elucidated in detail in the closely related locust species Schistocerca gregaria [10, 11]; this species lacks AKH III [12]. The signal peptide of the prepro-AKHs is co-translationally cleaved, generating pro-AKH. Subsequent proteolytic processing, which is preceded by the dimerization of two pro-AKHs (I/I, I/II, or II/II) at random by the formation of a disulphide bond resulting from the oxidation of the (single) cysteine residue in their AKH-associated peptides (AAPs) (see Fig. 1), gives rise to two AKHs (I and/or II) and one homo- or heterodimeric peptide, consisting of two AAPs (I/I, I/II, or II/II). Data from capillary liquid chromatography-tandem mass spectrometry analysis showed the AAPs of these dimeric peptides to be processed further to smaller peptides (AKH-joining peptide I and II [AKH-JP I and II], respectively) and a resulting dimeric peptide which is called AKH precursor-related peptide (APRP) [7, 13] (see Fig. 1). In L. migratoria, the additional production of AKH- III results in the formation of an APRP with two disulphide bonds, a homodimer resulting from the crosslinking (in a parallel and/or antiparallel fashion) of two AKH-III prohormone molecules [14] (see Fig. 1). A putative cleavage site within the sequence of the latter APRP is lacking, suggesting that this APRP likely is not processed further [14]. Figure 1: Sequence and proteolytic processing of Locusta migratoria AKH prohormones. The sequence of AKH-I, -II and -III is followed by a processing site (GKR or GRR, boxed in blue/red); identical residues in all three AKHs are connected by white lines. Identical residues in the AKH-associated peptides (AAPs) I and II are boxed. The cysteine residues forming disulfide bridges prior to proteolytic processing of all AKH prohormones (I/I, I/II or II/II; pro-AKH- III crosslinks only to III/ III) are shown in a red box. JP: joining peptide. (Based on data from [7, 13-14]; after [22]). Following their synthesis in the rough endoplasmic reticulum of the cell bodies of the adipokinetic cells, the adipokinetic prohormones are packaged into secretory granules at the trans-Golgi network, while proteolytic processing to the bioactive hormones is presumed to take place in the secretory granules (for
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
Page 2 and 3: Hemolymph Proteins and Functional P
Page 4 and 5: CONTENTS Foreword i Preface ii List
Page 6 and 7: ii PREFACE The aim of this eBook
Page 8 and 9: iv Giancarlo Lopez-Martinez Departm
Page 12 and 13: Hemolymph Lipoproteins: Role in Ins
Page 16 and 17: 32 Hemolymph Proteins and Functiona
Page 18 and 19: 34 HPFP: Recent Advances in Insects
Page 20 and 21: Immune Response of Insects and Crus
Page 22 and 23: 78 Hemolymph Proteins and Functiona
Page 24 and 25: 80 HPFP: Recent Advances in Insects
Page 26 and 27: Structures and Functions of Insect
Page 30 and 31: Neurohormones and Second Messengers
Page 32 and 33: Role of Conventional and Unconventi
Page 36 and 37: Insulin-Related Peptides in Insects
Page 38 and 39: ENF Peptides HPFP: Recent Advances

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