• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Oct 1, 2002; 367(Pt 1): 187–193.
PMCID: PMC1222869

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


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.

Full Text

The Full Text of this article is available as a PDF (228K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Corvol P, Williams TA, Soubrier F. Peptidyl dipeptidase A: angiotensin I-converting enzyme. Methods Enzymol. 1995;248:283–305. [PubMed]
  • Cornell MJ, Williams TA, Lamango NS, Coates D, Corvol P, Soubrier F, Hoheisel J, Lehrach H, Isaac RE. Cloning and expression of an evolutionary conserved single-domain angiotensin converting enzyme from Drosophila melanogaster. J Biol Chem. 1995 Jun 9;270(23):13613–13619. [PubMed]
  • Williams TA, Michaud A, Houard X, Chauvet MT, Soubrier F, Corvol P. Drosophila melanogaster angiotensin I-converting enzyme expressed in Pichia pastoris resembles the C domain of the mammalian homologue and does not require glycosylation for secretion and enzymic activity. Biochem J. 1996 Aug 15;318(Pt 1):125–131. [PMC free article] [PubMed]
  • Isaac R, Schoofs L, Williams TA, Veelaert D, Sajid M, Corvol P, Coates D. A novel peptide-processing activity of insect peptidyl-dipeptidase A (angiotensin I-converting enzyme): the hydrolysis of lysyl-arginine and arginyl-arginine from the C-terminus of an insect prohormone peptide. Biochem J. 1998 Feb 15;330(Pt 1):61–65. [PMC free article] [PubMed]
  • Taylor CA, Coates D, Shirras AD. The Acer gene of Drosophila codes for an angiotensin-converting enzyme homologue. Gene. 1996 Nov 28;181(1-2):191–197. [PubMed]
  • Houard X, Williams TA, Michaud A, Dani P, Isaac RE, Shirras AD, Coates D, Corvol P. The Drosophila melanogaster-related angiotensin-I-converting enzymes Acer and Ance--distinct enzymic characteristics and alternative expression during pupal development. Eur J Biochem. 1998 Nov 1;257(3):599–606. [PubMed]
  • Lamango NS, Isaac RE. Identification and properties of a peptidyl dipeptidase in the housefly, Musca domestica, that resembles mammalian angiotensin-converting enzyme. Biochem J. 1994 May 1;299(Pt 3):651–657. [PMC free article] [PubMed]
  • Lamango NS, Nachman RJ, Hayes TK, Strey A, Isaac RE. Hydrolysis of insect neuropeptides by an angiotensin-converting enzyme from the housefly, Musca domestica. Peptides. 1997;18(1):47–52. [PubMed]
  • Wijffels G, Fitzgerald C, Gough J, Riding G, Elvin C, Kemp D, Willadsen P. Cloning and characterisation of angiotensin-converting enzyme from the dipteran species, Haematobia irritans exigua, and its expression in the maturing male reproductive system. Eur J Biochem. 1996 Apr 15;237(2):414–423. [PubMed]
  • Isaac RE, Lamango NS. Peptidyl dipeptidase activity in the haemolymph of insects. Biochem Soc Trans. 1994 Aug;22(3):292S–292S. [PubMed]
  • Tatei K, Cai H, Ip YT, Levine M. Race: a Drosophila homologue of the angiotensin converting enzyme. Mech Dev. 1995 Jun;51(2-3):157–168. [PubMed]
  • Rusch J, Levine M. Regulation of a dpp target gene in the Drosophila embryo. Development. 1997 Jan;124(2):303–311. [PubMed]
  • Ashe HL, Levine M. Local inhibition and long-range enhancement of Dpp signal transduction by Sog. Nature. 1999 Apr 1;398(6726):427–431. [PubMed]
  • Isaac RE, Ekbote U, Coates D, Shirras AD. Insect angiotensin-converting enzyme. A processing enzyme with broad substrate specificity and a role in reproduction. Ann N Y Acad Sci. 1999;897:342–347. [PubMed]
  • Thummel CS. Flies on steroids--Drosophila metamorphosis and the mechanisms of steroid hormone action. Trends Genet. 1996 Aug;12(8):306–310. [PubMed]
  • Quan GX, Mita K, Okano K, Shimada T, Ugajin N, Xia Z, Goto N, Kanke E, Kawasaki H. Isolation and expression of the ecdysteroid-inducible angiotensin-converting enzyme-related gene in wing discs of Bombyx mori. Insect Biochem Mol Biol. 2001 Jan;31(1):97–103. [PubMed]
  • Andres AJ, Thummel CS. Methods for quantitative analysis of transcription in larvae and prepupae. Methods Cell Biol. 1994;44:565–573. [PubMed]
  • Lamango N, Isaac RE. Identification of an ACE-like peptidyl dipeptidase activity in the housefly, Musca domestica. Biochem Soc Trans. 1993 Aug;21(3):245S–245S. [PubMed]
  • Siviter RJ, Coast GM, Winther AM, Nachman RJ, Taylor CA, Shirras AD, Coates D, Isaac RE, Nässel DR. Expression and functional characterization of a Drosophila neuropeptide precursor with homology to mammalian preprotachykinin A. J Biol Chem. 2000 Jul 28;275(30):23273–23280. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Henrich VC, Tucker RL, Maroni G, Gilbert LI. The ecdysoneless (ecd1ts) mutation disrupts ecdysteroid synthesis autonomously in the ring gland of Drosophila melanogaster. Dev Biol. 1987 Mar;120(1):50–55. [PubMed]
  • Thummel CS. Steroid-triggered death by autophagy. Bioessays. 2001 Aug;23(8):677–682. [PubMed]
  • Richards G. The radioimmune assay of ecdysteroid titres in Drosophila melanogaster. Mol Cell Endocrinol. 1981 Mar;21(3):181–197. [PubMed]
  • Jiang C, Baehrecke EH, Thummel CS. Steroid regulated programmed cell death during Drosophila metamorphosis. Development. 1997 Nov;124(22):4673–4683. [PubMed]
  • Berreur P, Porcheron P, Moriniere M, Berreur-Bonnenfant J, Belinski-Deutsch S, Busson D, Lamour-Audit C. Ecdysteroids during the third larval instar in 1(3)ecd-1ts, a temperature-sensitive mutant of Drosophila melanogaster. Gen Comp Endocrinol. 1984 Apr;54(1):76–84. [PubMed]
  • Pino-Heiss S, Schubiger G. Extracellular protease production by Drosophila imaginal discs. Dev Biol. 1989 Apr;132(2):282–291. [PubMed]
  • Appel LF, Prout M, Abu-Shumays R, Hammonds A, Garbe JC, Fristrom D, Fristrom J. The Drosophila Stubble-stubbloid gene encodes an apparent transmembrane serine protease required for epithelial morphogenesis. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4937–4941. [PMC free article] [PubMed]
  • Ohtsuki S, Homma K, Kurata S, Komano H, Natori S. A prolyl endopeptidase of Sarcophaga peregrina (flesh fly): its purification and suggestion for its participation in the differentiation of the imaginal discs. J Biochem. 1994 Mar;115(3):449–453. [PubMed]
  • Ohtsuki S, Homma K, Kurata S, Natori S. Molecular cloning of cDNA for Sarcophaga prolyl endopeptidase and characterization of the recombinant enzyme produced by an E. coli expression system. Insect Biochem Mol Biol. 1997 Apr;27(4):337–343. [PubMed]
  • Amin A, Li Y, Finkelstein R. Identification of a Drosophila prolyl endopeptidase and analysis of its expression. DNA Cell Biol. 1999 Aug;18(8):605–610. [PubMed]
  • Zhao X, Mita K, Shimada T, Okano K, Quan GX, Kanke E, Kawasaki H. Isolation and expression of an ecdysteroid-inducible neutral endopeptidase 24.11-like gene in wing discs of Bombyx mori. Insect Biochem Mol Biol. 2001 Nov 1;31(12):1213–1219. [PubMed]
  • Turner AJ, Isaac RE, Coates D. The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Bioessays. 2001 Mar;23(3):261–269. [PubMed]
  • Hall NA. Peptidases in Drosophila melanogaster. I. Characterization of dipeptidase and leucine aminopeptidase activities. Biochem Genet. 1986 Oct;24(9-10):775–793. [PubMed]
  • Haunerland NH. Insect storage proteins: gene families and receptors. Insect Biochem Mol Biol. 1996 Sep-Oct;26(8-9):755–765. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...