CAENORHABDITIS-ELEGANS CONTAINS 2 DISTINCT ACID SPHINGOMYELINASES

Mounting evidence supports a role for acid sphingomyelinase (ASM) in c ellular 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 t his study, we show that the nematode Caenorhabditis elegans possesses two ASMs, termed ASM-1 and ASM-2 encoded by two distinct genes, but la cks 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 site s, are conserved, The expression of these genes in C. elegans is regul ated during development Asm-l is preferentially expressed in the embry o, whereas asm-2 is predominantly expressed in postembryonic stages. W hets transfected as Flag-tagged proteins into COS-7 cells, ASM-P is fo und almost entirely in a secreted form whereas only 20% of ASM-2 is se creted. Only the secreted forms display enzymatic activity. Furthermor e, ASM-S requires addition of Zn2+ to be fully active, whereas ASM-B i s active in the absence of cation, C., elegans is the first organism t o display two ASMs. This finding suggests the existence of an ASM gene family.