Review
Does corazonin signal nutritional stress in insects?

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Abstract

The undecapeptide corazonin, initially discovered from the American cockroach as a strong cardioaccelerator, is now known to be ubiquitously present in arthropods, although it is absent from some species, notably Coleoptera. The structure of its precursor is similar to the GnRH precursor, while it acts through a receptor related to the GnRH receptor; corazonin thus appears to be an arthropod homolog of GnRH. It is produced by neuroendocrine cells in the brain, as well as interneurons in the ventral nerve cord. These two cell types are generally present in insects; in most species there are also other neurons producing corazonin. Its function in insects has remained obscure; its cardioacceleratory effects are limited to a few cockroach species, while in other species different physiological effects have been described. Most spectacularly it induces changes associated with the gregarious phase in migratory locusts and in the silkworm it reduces the size of the cocoon formed. Corazonin is able to induce ecdysis in two moth species, however locusts and flies in which the corazonin gene is no longer expressed, ecdyse normally and, hence, it is not clear whether corazonin is essential for ecdysis. As the corazonin neuroendocrine cells in the brain express receptors for two midgut peptides, it seems likely that their activity is modulated by the midgut endocrine cells. I propose that in insects corazonin might be released under conditions of nutritional stress, which can explain several of the observed physiological effects of this neurohormone.

Introduction

The insect adipokinetic, hyperglycemic and hypetrehalosemic hormones are octa-, nona- and deca-peptides which stimulate the mobilization of energy substrates from the fat body into the hemolymph. In most species these hormones stimulate glycogen phosphorylase, which leads to an increase in trehalose production, however this does not always lead to increased hemolymph concentrations of trehalose. In some species, fat is mobilized from the fat body, resulting in an increase in hemolymph lipids, in yet other species the production of proline from alanine is stimulated and hemolymph proline augments after release of these hormones (Gäde, 1990). Collectively these hormones are called adipokinetic hormones. What is fascinating about this hormone family is that of all the small insect neuropeptides this one shows by far the largest structural variability and many insect species have more than one AKH gene. This is all the more surprising as the homologous red pigment concentrating hormone (RPCH) from crustaceans does not show such a large structural variability. It has been suggested that this structural variability is related to and may have its origin in the variability of the use of different energy substrates (Veenstra and Camps, 1990).

Two octapeptide hyperglycemic hormones had already been identified from the corpora cardiaca of the American cockroach, Periplaneta americana (Scarborough et al., 1984), but decapeptides are also strongly hyperglycemic when injected into this species (e. g. Gäde, 1988). Since several insect species have both an octapeptide and a decapeptide AKH (Gäde, 1990), I suspected that P. americana might also have a decapeptide. This led to the search for a hyperglycemic decapeptide in this species and the identification of the undecapeptide corazonin, which had no hyperglycemic activity, but was remarkably active on the isolated heart preparation. Hence it was called corazonin from corazon, Spanish for heart (Veenstra, 1989a). Twenty years later it seems worthwhile to summarize what we know and what we don't know about this nearly ubiquitous arthropod neuropeptide.

Section snippets

Peptide structure

Once the structure of the peptide was determined (Fig. 1), it became clear that its structural similarities with members of the AKH peptide family were rather limited. Although a casual resemblance to GnRH was also noted, it was considered coincidental at the time. We now know that these similarities are probably not due to chance, as the insect corazonin and AKH receptors are closely related to the GnRH receptors (Park et al., 2002, Cazzamali et al., 2002, Belmont et al., 2006). Ligand

Gene structure

A preprocorazonin can be predicted from various insect genomes as well as from the genome of the tick I. scapularis (unpubl. data) and the cDNAs of various crustaceans and of another tick species (Genbank accession number EU622494). The preprohormone consists of the signal peptide, followed by corazonin, a convertase cleavage site and what has been called the corazonin-associated peptide. The only conserved part of the precursor is the part encoding corazonin and its convertase cleavage site,

Corazonin neuroendocrine cells and neurons

Expression of the corazonin gene has been studied in a variety of insect species by immunohistology (Veenstra and Davis, 1993, Cantera et al., 1994, Predel et al., 1994, Schoofs et al., 2000, Hansen et al., 2001, Siegmund and Korge, 2001, Roller et al., 2003, Roller et al., 2006, Hamanaka et al., 2004, Sehadová et al., 2007, Závodská et al., 2008, Závodská et al., 2009, Wen and Lee, 2008) as well as by in situ hybridization (Hansen et al., 2001, Choi et al., 2005) and transgenic Drosophila in

Corazonin receptor

The corazonin receptor has been identified by functional expression in Drosophila, M. sexta and Anopheles gambiae (Park et al., 2002, Cazzamali et al., 2002, Belmont et al., 2006). The Drosophila receptor has an EC50 of 1.1 nM (Park et al., 2002) and the M. sexta receptor EC50 of 200 pM when expressed in Xenopus oocytes (Kim et al., 2004). Genes coding orthologous proteins that almost certainly are functional corazonin receptors have been detected in the genome of the honey bee (Hauser et al.,

Biological effects

Corazonin was found to stimulate the frequency of the isolated heart of the American cockroach at low concentrations (Veenstra, 1989a). However, this effect is limited to a small number of cockroach species (Predel et al., 1994), and furthermore this cardioacceleratory effect is not found when injecting it into intact insects (Sláma et al., 2006). The denervated hyperneural muscle in P. americana is very sensitive to corazonin, at a threshold of 0.1 nM, but in nine other cockroach species it

A hormone in search of a function

Although there are quite a few physiological effects for corazonin, there is so far not a general physiological function attributed to this hormone. One would expect that the prominent corazonin neuroendocrine cells in the brain as well as the segmentally repeated interneurons in the ventral nerve cord, which are clearly homologous in the various insect species, have a similar if not the same functions in different insect species. It has been suggested that the ventral interneurons might take

Conclusion

The release of corazonin during nutritional stress would allow a logical connection between various physiological effects described for this neurohormone, and, therefore, seems an attractive hypothesis.

Acknowledgments

I thank all those who at one time or another contributed to my work on corazonin, in particular Teresa Martinez for encouragement throughout all these years, Yuetian Chen, who tested corazonin on hearts of pharate Manduca sexta, Norman Davis who showed me the beauty of wholemount fluorescence preparations, Rafael Cantera for insisting on and convincing me of the direct innervation of the crop duct in Phormia terranovae, Tim Kingan for suggesting me to use competitive ELISAs, José Roberto

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