Allatostatin C and its paralog allatostatin double C: The arthropod somatostatins

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Abstract

Arthropods do not have one, but two genes encoding an allatostatin C-like peptide. The newly discovered paralog gene was called Ast-CC, and the peptide which it is predicted to make was called allatostatin double C (ASTCC). Genes for both allatostatin C (ASTC) and its paralog were found in the tick Ixodes scapularis as well as dipteran, lepidopteran, coleopteran, aphidoidean and phthirapteran insect species. In addition partial or complete cDNAs derived from Ast-CCs were found in a number of species, including Drosophila melanogaster, Bombyx mori and Rhodnius prolixus. The ASTCC precursors have a second conserved peptide sequence suggesting that they may produce two biologically active peptides. The predicted precursors encoded by the Ast-CCs have some unusual features, particularly in Drosophila, where they lack a signal peptide, and have instead a peptide anchor. These unusual structural features suggest that they are perhaps expressed by cells that are not specialized in neuropeptide synthesis and that in Drosophila ASTCC may be a juxtacrine. Data from the Fly Atlas project show that in Drosophila Ast-CC is little expressed. Nevertheless a P-element insertion in this gene is embryonic lethal, suggesting that it is an essential gene. Similarity between the precursors and receptors of ASTC/ASTCC and somatostatin suggests that ASTC/ASTCC and somatostatin have a common ancestor.

Introduction

The sesquiterpenoid juvenile hormone is produced by the corpora allata and exercises essential functions in insect growth, metamorphosis and reproduction (e.g. Feyereisen, 1985). The regulation of the biosynthetic activity of the corpora allata has been studied extensively and it is known that the activity of the corpora allata is at least in part regulated by neuropeptides, which may either stimulate (allatotropins) or inhibit (allatostatins) the corpora allata to synthesize juvenile hormone. The first allatostatins identified were isolated from the cockroach Diploptera punctata (Woodhead et al., 1989, Pratt et al., 1991), but it became soon apparent that these peptides and their homologs are present in many insect species (e.g. Duve et al., 1993, Veenstra et al., 1997, Davis et al., 1997) as well as other arthropods (Duve et al., 1997). Furthermore they are not only produced by the brain to inhibit the activity of the corpora allata, but they are also produced by other tissues, notably the midgut from where they could potentially be released in concentrations sufficient to inhibit the corpora allata (Reichwald et al., 1994). It thus appears, that like the somatostatins in vertebrates, the allatostatins are general inhibitory peptides used for different functions.

The identification of allatostatins from other insect species has been pursued by both immunoassay using antisera to the peptides identified from Diploptera as well as the synthetic activity of the corpus allatum to identify allatostatins. These bioassays yielded other neuropeptides with allatostatic activity. Unfortunately, though these peptides were clearly structurally different from the allatostatins from Diploptera, they were also given the name allatostatin. Thus from the cricket Gryllus bimaculatus a number of neuropeptides were identified (Lorenz et al., 1995) having allatostatic activity; these are commonly called allatostatins B to distinguish them from the allatostatins identified from Diploptera, now called allatostatins A. From the tobacco hornworm moth Manduca sexta yet another allatostatin was identified (Kramer et al., 1991), a peptide now known as allatostatin C (ASTC). As is the case for the allatostatins A, the allatostatins B and C are also present in other insect species, e.g. Drosophila melanogaster (Williamson et al., 2001, Price et al., 2002), Aedes aegypti (Li et al., 2006) and Tribolium castaneum (Li et al., 2008) and in different tissues, notably again in the midgut (Veenstra et al., 2008).

While the allatostatins A and B are produced from precursors producing from three to fourteen structurally related peptides (Taghert and Veenstra, 2003), the known ASTC genes encode a single biologically peptide. ASTC seems very well conserved; from several lepidopteran species cDNAs have been isolated (Jansons et al., 1996, Abdel-latief et al., 2003, Sheng et al., 2007) predicting the same peptide as the one initially isolated from Manduca (Kramer et al., 1991). The ASTC predicted from the Drosophila genome differs from the Manduca peptide in a single amino acid residue (Williamson et al., 2001, Price et al., 2002); the ASTC isolated from A. aegypti adds a second substitution (Li et al., 2006), as does the peptide predicted and tentatively identified by mass spectrometry from Tribolium (Li et al., 2008). It was therefore somewhat of a surprise to see the honeybee peptide to be significantly different; so different in fact that it was not recognized by the authors as an ASTC (Hummon et al., 2006). The peptide inhibits the synthesis of juvenile hormone in the moths M. sexta and Helicoverpa zea (Kramer et al., 1991) as well as the mosquito A. aegypti (Li et al., 2006), but it is much less effective in other moth species (Jansons et al., 1996, Audsley et al., 1999), and does not inhibit the corpora allata in D. melanogaster (Price et al., 2002). However, in the latter species it does inhibit the rate of heartbeat (Price et al., 2002).

Although so far genomic analysis has only revealed a single allatostatin A, B or C gene per species, analysis of the various insect genomes which have been, or are in the progress of being sequenced, revealed that all these insect species have in fact not one but two genes encoding an ASTC-like peptide. These two genes were also found in the genome of the tick Ixodes scapularis and may thus well be generally present in arthropods. The predicted precursor of the second gene has some unusual features, particularly in Drosophila.

Section snippets

Genome analysis

The genomes of D. melanogaster, Drosophila simulans, Drosophila sechellia, Drosophila yakuba, Drosophila erecta, Drosophila ananassae, Drosophila persimilis, Drosophila willistoni, Drosophila grimshawi, Drosophila virilis, Drosophila pseudoobscura, Drosophila mojavensis, Glossina morsitans, Anopheles gambiae, A. aegypti, Culex pipiens, Bombyx mori, T. castaneum, Apis mellifera, Nasonia vitripennis, Pediculus humanus corporis, Acyrthosiphon pisum and I. scapularis were analyzed using the BLAST

Two genes encoding an ASTC-like peptide

The Drosophila genome contains two genes encoding ASTC-like peptides, the previously described Ast-C (CG14919, Williamson et al., 2001) and Ast-CC (CG14920) described here. In all insect species with a reasonably complete sequenced genome as well as in the tick I. scapularis two genes encoding ASTC-like peptides were also found (Fig. 1, Fig. 2). The peptide encoded by the newly discovered gene was called allatostatin CC (double C) and its gene Ast-CC to emphasize its strong structural

Two arthropod genes coding ASTC-like peptides

Two genes encoding ASTC-like peptides appear commonly present in arthropods. That no such genes were found in vertebrates is hardly surprising. Primary sequences of small neuropeptides are often poorly conserved during evolution, as e.g. in the case of the sulfakinins and locustatachykinins, which are in all likelihood evolutionarily related to the vertebrate cholecystokinin and tachykinin peptide families, respectively (Taghert and Veenstra, 2003). However, the primary sequences of their

Acknowledgements

I thank Rob Weaver for pointing out some ASTC and ASTCC sequences I had missed. I thank him, Paul Taghert and four anonymous reviewers for making constructive criticism on the manuscript, and I also thank all those who sequenced the genomes and produced the websites and programs making their access and analysis possible.

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