CGC Bibliography Paper 3086

Caenorhabditis elegans contains two distinct acid sphingomyelinases.

Lin X, Hengartner MO, Kolesnick R

Medline:

98269102

Citation:

Journal of Biological Chemistry 273: 14374-14379 1998

Type:

ARTICLE

Genes:

asm-1 asm-2

Abstract:

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-l 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-P 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-S requires addition of Zn2+ to be fully active, whereas ASM-B 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.