ReviewDoes corazonin signal nutritional stress in insects?
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
References (94)
- et al.
Specification of neuropeptide cell identity by the integration of retrograde BMP signaling and a combinatorial transcription factor code
Cell
(2003) - et al.
Identification of four evolutionarily related G protein-coupled receptors from the malaria mosquito Anopheles gambiae
Biochem. Biophys. Res. Commun.
(2006) - et al.
Immunocytochemical analysis of putative allatostatin receptor (DAR-2) distribution in the CNS of larval Drosophila melanogaster
Peptides
(2005) - et al.
Molecular cloning and functional expression of a Drosophila corazonin receptor
Biochem. Biophys. Res. Commun.
(2002) Neuropeptide discovery in Ixodoidea: an in silico investigation using publicly accessible expressed sequence tags
Gen. Comp. Endocrinol.
(2008)The release by feeding of pharmacologically active factor from the corpus cardiacum of Periplaneta americana
J. Insect Physiol.
(1962)- et al.
Specification and development of the pars intercerebralis and pars lateralis, neuroendocrine command centers in the Drosophila brain
Dev. Biol.
(2007) - et al.
Effects of an allatostatin and a myosuppressin on midgut carbohydrate enzyme activity in the cockroach Diploptera punctata
Peptides
(1999) The adipokinetic hormone red pigment-concentrating hormone peptide family – structures, interrelationships and functions
J. Insect Physiol.
(1990)- et al.
Predicted versus expressed adipokinetic hormones, and other small peptides from the corpus cardiacum–corpus allatum: a case study with beetles and moths
Peptides
(2008)