Sphingosine-1-phosphate phosphatase (SPP) catalyzes the dephosphorylation of sphingosine-1-phosphate (S1P) into sphingosine, the reverse reaction of sphingosine kinase. In mammals, S1P acts as a potent bioactive molecule regulating cell proliferation, migration, and immunity. In Leishmania, S1P production is crucial for the synthesis of ethanolamine and choline phospholipids, and cell survival under stress conditions. To better understand the roles of S1P, we characterized a SPP ortholog in Leishmania major which displays activity towards S1P but not structurally related lipids such as ceramide-1-phosphate or lysophosphatidic acid. While this enzyme is found in the endoplasmic reticulum in mammalian cells, L. major SPP is localized at the Golgi apparatus. Importantly, chromosomal SPP alleles cannot be deleted from L. major even with the addition of a complementing episome, suggesting that endogenously expressed SPP is essential. Finally, SPP overexpression in L. major leads to a slower growth rate and heightened sensitivity to brefeldin A and sodium orthovanadate. Together, these results suggest that the equilibrium between S1P and sphingosine is vital for the function of Golgi apparatus in Leishmania.
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| http://dx.doi.org/10.1038/s41598-022-20249-w | DOI Listing |
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