Ance, a Drosophila angiotensin-converting enzyme homologue, is expressed in imaginal cells during metamorphosis and is regulated by the steroid, 20-hydroxyecdysone

Abstract

Ance is a single domain homologue of mammalian angiotensin-converting enzyme (ACE) and is important for normal development and reproduction in Drosophila melanogaster. Mammalian ACE is responsible for the synthesis of angiotensin II and the inactivation of bradykinin and N -acetyl-Ser-Asp-Lys-Pro, but the absence of similar peptide hormones in insects suggests novel functions for Ance. We now provide evidence in support of a role for Ance during Drosophila metamorphosis. The transition of larva to pupa was accompanied by a 3-fold increase in ACE-like activity, which subsequently dropped to larval levels on adult eclosion. This increase was attributed to the induction of Ance expression during the wandering phase of the last larval instar in the imaginal cells (imaginal discs, abdominal histoblasts, gut imaginal cells and imaginal salivary gland). Ance expression was particularly strong in the presumptive adult midgut formed as a result of massive proliferation of the imaginal midgut cells soon after pupariation. No Ance transcripts were detected in the midgut of the fully differentiated adult intestine. Ance protein and mRNA were not detected in imaginal discs from wandering larvae of flies homozygous for the ecd ( 1 ) allele, a temperature-sensitive ecdysone-less mutant, suggesting that Ance expression is ecdysteroid-dependent. Physiological levels of 20-hydroxyecdysone induced the synthesis of ACE-like activity and Ance protein by a wing disc cell line (Cl.8+), confirming that Ance is an ecdysteroid-responsive gene. We propose that the expression of Ance in imaginal cells is co-ordinated by exposure to ecdysteroid (moulting hormone) during the last larval instar moult to increase levels of ACE-like activity during metamorphosis. The enzyme activity may be required for the processing of a developmental peptide hormone or may function in concert with other peptidases to provide amino acids for the synthesis of adult proteins.

The angiotensin converting enzyme inhibitor captopril reduces oviposition and ecdysteroid levels in Lepidoptera

“…Quan et al (1998) reported that BmAcer expression is ecdysone-inducible. A 20E-induced synthesis of ACE-like activity was also observed in D. melanogaster (Siviter et al, 2002) and in A. stephensi (Ekbote et al, 1999). Moreover, Loeb et al (1998) demonstrated that ACE-activity stimulates ecdysteroid synthesis, perhaps due to feedback effects.…”

“…Siviter et al (2002) previously suggested such a role for ACE based on their findings that larvalpupal transition of D. melanogaster was accompanied by a 3-fold increase in ACE-activity. This increase was attributed to the strong induction of Ance expression in the imaginal cells by 20E.…”

“…Several recent studies provide evidence for reciprocal interactions between ACE and ecdysteroid production (Loeb et al, 1998;Quan et al, 2001;Vandingenen et al, 2001;Siviter et al, 2002). Quan et al (1998) reported that BmAcer expression is ecdysone-inducible.…”

“…More evidence in support of a role for ACE in metamorphosis was provided by Siviter et al (2002). During pupal development of D. melanogaster, ACE-like activity increased 3-fold at a mid-pupal stage, before declining to larval levels at the time of adult eclosion (Siviter et al, 2002).…”

The secreted salivary proteome of the pea aphid Acyrthosiphon pisum characterised by mass spectrometry

“…The first was matched to ACE (peptidyl dipeptidase A, EC 3.4.15.1), a member of the M2-metallopeptidase family, and was demonstrated in the in-solution digested sample and in the 110-and 100-kDa bands of the 1-DE secreted saliva. ACE have been described as nonspecific dipeptydyl carboxypeptidases [28] and have been characterised in a number of insects, including Bombyx mori, D. melanogaster, L. migratoria, Musca domestica, and S. littoralis [29][30][31][32][33]. In insects, ACE are thought to be involved in regulating peptide hormones and neuropeptides by removing dipeptides, dipeptideamides and tripeptideamides from the C terminus of short peptides ( [31,32,34,35], reviewed in [36]).…”