The drosophila angiotensin-converting enzyme homologue Ance is required for spermiogenesis

Abstract

The Angiotensin-converting enzyme (Ance) gene of Drosophila melanogaster is a homologue of mammalian angiotensin-converting enzyme (ACE), a peptidyl dipeptidase implicated in regulation of blood pressure and male fertility. In Drosophila, Ance protein is present in vesicular structures within spermatocytes and immature spermatids. It is also present within the lumen of the testis and the waste bag, and is associated with the surface of elongated spermatid bundles. Ance mRNA is found mainly in large primary spermatocytes and is not detectable in cyst cells. Testes lacking germ cells have reduced levels of ACE activity, and no Ance protein is detectable by immunocytochemistry, indicating that the germ cells are the major site of Ance synthesis. Ance mutant testes lack individualised sperm and have very few actin-based individualisation complexes. Spermatid nuclei undergo scattering along the cyst and have abnormal morphology, similar to other individualisation mutants. Mutant spermatids also have abnormal ultrastructure with grossly defective mitochondrial derivatives. The failure of Ance mutant testes to form individualisation complexes may be due to a failure in correct spermatid differentiation. Taken together, the expression pattern and mutant phenotype suggest that Ance is required for spermatid differentiation, probably through the processing of a regulatory peptide synthesised within the developing cyst.

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

“…Also, chicken (Gallus gallus) lacks testis ACE expression so that the physiologic requirement for testis ACE does not appear absolute (Esther et al, 1994). ACE, however, has been implicated in playing an important role in the fertility of insects and oysters (Ekbote et al, 2003;Hurst et al, 2003;Riviere et al, 2011). Thus, the role of ACE in reproduction may have played an important role in maintaining the structure of at least one of the two domains.…”

Agm1/Pgm3-Mediated Sugar Nucleotide Synthesis Is Essential for Hematopoiesis and Development

“…At present, it is unclear how aberrant glycosylation of ACE contributes to the defective spermatogenesis observed in Pgm3 mld1/mld1 and Pgm3 mld1gt mice. Inactivation of Ace in the mouse leads to male hypofertility, and the homologue in Drosophila melanogaster is required for spermiogenesis (18). However, unlike Pgm3 mld1/mld1 and Pgm3 mld1/gt mice, Ace-deficient mice have normal numbers of sperm (12,13,20).…”

Male accessory glands of Drosophila melanogaster make a secreted angiotensin I-converting enzyme (ANCE), suggesting a role for the peptide-processing enzyme in seminal fluid

“…The final volume was made up to 260·l with 0.1% (v/v) trifluoracetic acid and the released hippuric acid was quantified by HPLC using a 5· C18 (150·mmϫ4.6·mm) column, as described previously (Lamango et al, 1996). Immunoelectrophoresis AG proteins from both Oregon R and tudor (tud) flies were extracted and separated on a 10% sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gel, transferred to a PVDF membrane, and then incubated with anti-ANCE antibody at a 1:5000 dilution in PBST, 5% (w/v) nonfat dried milk powder as described previously (Houard et al, 1998;Hurst et al, 2003). Bound anti-ANCE antibody was detected by using a horseradish peroxidase-conjugated sheep anti-rabbit Fc antibody and the Enhanced Chemiluminescence Detection Kit (Amersham Pharmacia Biotech Ltd., UK) as described in the manufacturer's instructions.…”

“…In the testes of Drosophila melanogaster, germ cells are the major site of ACE (known as ANCE) biosynthesis and male flies homozygous for hypomorphic alleles of Ance are infertile (Tatei et al, 1995). This infertility results from a failure in spermiogenesis, suggesting that one of the functions of germinal ANCE in D. melanogaster is the processing of a regulatory peptide required for spermatid differentiation (Hurst et al, 2003). Another possible role for ANCE is in the processing of peptides in Angiotensin I-converting enzyme (ACE) expressed on the surface of endothelial cells is responsible for the last step in the synthesis of circulating angiotensin II and the inactivation of bradykinin.…”