Transmembrane topology of sphingoid long-chain base-1-phosphate phosphatase, Lcb3p - PubMed (original) (raw)
Transmembrane topology of sphingoid long-chain base-1-phosphate phosphatase, Lcb3p
Akio Kihara et al. Genes Cells. 2003 Jun.
Free article
Abstract
Background: Sphingoid long-chain base-1-phosphates (LCBPs) are thought to act as intracellular signalling molecules in yeast. Lcb3p is a member of the LCBPs-specific phosphatase family (SPP family). Other yeast phosphatases, Lpp1p and Dpp1p, are members of a different lipid phosphatase family (LPP family) known to exhibit broader substrate specificities. Until now, only the membrane topology of mammalian LPP family members has been reported, whereas that of the SPP family has remained unclear.
Results: In our in vitro system, Lcb3p displayed major phosphatase activity against dihydrosphingosine-1-phosphate, while Dpp1p and Lpp1p also exhibited activities. Here, we determined that Lpp1p and Dpp1p exhibit the topology common to the LPP family. Moreover, we examined the transmembrane topology of Lcb3p using a C-terminal reporter approach. From our results we deduced a structural model illustrating that Lcb3p has eight membrane-spanning domains with its highly conserved phosphatase motifs positioned within the endoplasmic reticulum (ER) lumen. Consistent with this result, Lcb3p collected in low speed pellet fractions was highly resistant to exogenous proteinase K unless the membrane was disrupted.
Conclusion: Our results suggest that the active site of Lcb3p is located in the ER lumen and, thus, the phosphate group of the LCBP is hydrolysed on the lumenal side.
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