Disease relevance of Sacy

• Here, we show that targeted disruption of the sAC gene does not affect spermatogenesis but dramatically impairs sperm motility, leading to male sterility. sAC mutant spermatozoa are characterized by a total loss of forward motility and are unable to fertilize oocytes in vitro [1].

High impact information on Sacy

• Interestingly, motility in sAC mutant spermatozoa can be restored on cAMP loading, indicating that the motility defect observed is not caused by a structural defect [1].
• Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect [1].
• Our findings reveal an essential role of Ae2 in mouse spermiogenesis and stress the recently postulated involvement of bicarbonate in germ-cell differentiation through the bicarbonate-sensitive soluble-adenylyl-cyclase pathway [2].
• Bicarbonate ions activated both sAC forms and increased cAMP levels in germ cells isolated from 25- and 50-day-old rats and adult rats in a concentration-dependent manner [3].
• These findings provide evidence that full-length and truncated sAC are generated by alternate splicing [3].

Biological context of Sacy

• The truncated sAC transcript lacks exon 11 with a premature termination of the open reading frame after the catalytic domain [3].
• Elevated levels of sAC mRNA are first observed in pachytene spermatocytes and expression increases through spermiogenesis [4].
• The accumulation of high levels of message in round spermatids suggests sAC protein plays an important role in the generation of cAMP in spermatozoa, implying possible roles in sperm maturation through the epididymis, capacitation, hypermotility, and/or the acrosome reaction [4].
• This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC [5].
• The immotility phenotype of the sNHE null spermatozoa appears to result from an intimate association of sNHE and the atypical adenylyl cyclase (sAC), while a failure of calcium entry requiring an apparent CatSper1 and -2 heteromeric ion channel correlates with a hyperactivation defect in these null animals [6].

Anatomical context of Sacy

• Identification and functional analysis of splice variants of the germ cell soluble adenylyl cyclase [3].

Associations of Sacy with chemical compounds

• HCO(3)(-) is unable to rapidly accelerate the flagellar beat or facilitate evoked Ca(2+) entry into sAC(-/-) spermatozoa [7].
• Gene database searches identified sAC homologues in species known to have cyclic AMP-dependent sperm motility [8].

Other interactions of Sacy

• In addition to a bicarbonate-regulated soluble adenylyl cyclase (sAC), mammalian spermatozoa, like somatic cells, appear to contain receptor/G protein-regulated AC activity that contributes to the modulation of specialized cell processes [9].

Analytical, diagnostic and therapeutic context of Sacy

• Two different transcripts encoding a full-length and truncated sAC were identified by reverse transcriptase-polymerase chain reaction and RNase protection analysis [3].
• The presence of corresponding proteins in testis, germ cells, and spermatozoa was demonstrated by fast protein liquid chromatography and differential immunoprecipitation with full-length sAC-specific antibodies [3].

References