Functions of neutral ceramidase in the Golgi apparatus.

Journal of Lipid Research
Wataru SakamotoYusuf A Hannun

Abstract

Ceramidases hydrolyze ceramides into sphingosine and fatty acids, with sphingosine being further metabolized into sphingosine-1-phosphate (S1P); thus, ceramidases control the levels of these bioactive sphingolipids in cells and tissues. Neutral ceramidase (nCDase) is highly expressed in colorectal tissues, and a recent report showed that nCDase activity is involved in Wnt/β-catenin signaling. In addition, the inhibition of nCDase decreases the development and progression of colorectal tumor growth. Here, to determine the action of nCDase in colorectal cancer cells, we focused on the subcellular localization and metabolic functions of this enzyme in HCT116 cells. nCDase was found to be located in both the plasma membrane and in the Golgi apparatus, but it had minimal effects on basal levels of ceramide, sphingosine, or S1P. Cells overexpressing nCDase were protected from the cell death and Golgi fragmentation induced by C6-ceramide, and they showed reduced levels of C6-ceramide and higher levels of S1P and sphingosine. Furthermore, compartment-specific metabolic functions of the enzyme were probed using C6-ceramide and Golgi-targeted bacterial SMase (bSMase) and bacterial ceramidase (bCDase). The results showed that Golgi-specif...Continue Reading

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Citations

Aug 21, 2020·Science Translational Medicine·Sarah AlsammanJennifer Y Chen
Jun 28, 2019·Journal of Lipid Research·Wataru SakamotoYusuf A Hannun
Dec 11, 2019·Cells·Farzana ParveenLiang-Yin Ke
Apr 16, 2020·Cancer Research·Line PedersenNils Halberg
Dec 3, 2020·Metabolites·Peeranat JatooratthawichotJames R Ketudat Cairns
Jul 11, 2021·Cellular Signalling·Real Sumayya Abdul SattarSundeep Singh Saluja
Aug 7, 2021·Medicina·Ana Gomez-LarrauriAlberto Ouro

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