Caenorhabditis elegans contains two distinct acid sphingomyelinases.
Mounting evidence supports a role for acid sphingomyelinase (ASM) in cellular stress signaling. Only murine and human sphingomyelinases have been defined at the molecular level. These enzymes are the products of a conserved gene and at the amino acid level share 82% identity. In this study, we show that the nematode Caenorhabditis elegans possesses two ASMs, termed ASM-1 and ASM-2 encoded by two distinct genes, but lacks detectable neutral sphingomyelinase activity. The C. elegans ASMs are about 30% identical with each other and with the human and murine enzymes. The conserved regions include a saposin-like domain, proline-rich domain, and a putative signal peptide. In addition, 16 cysteines distributed throughout the molecules, and selected glycosylation sites, are conserved. The expression of these genes in C. elegans is regulated during development. Asm-1 is preferentially expressed in the embryo, whereas asm-2 is predominantly expressed in postembryonic stages. When transfected as Flag-tagged proteins into COS-7 cells, ASM-1 is found almost entirely in a secreted form whereas only 20% of ASM-2 is secreted. Only the secreted forms display enzymatic activity. Furthermore, ASM-2 requires addition of Zn2+ to be fully active, whereas ASM-1 is active in the absence of cation. C. elegans is the first organism to display two ASMs. This finding suggests the existence of an ASM gene family.
Lin
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Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Hengartner
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Kolesnick
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D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000201:enzymology*; D002412:Cations / Q000494:pharmacology; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D015870:Gene Expression / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry*; D014162:Transfection / Q000235:genetics; D015032:Zinc / Q000494:pharmacology
D002412:Cations; D012333:RNA, Messenger; C112980:acid sphingomyelinase-1; C112981:acid sphingomyelinase-2; D013108:Sphingomyelin Phosphodiesterase; D015032:Zinc