Characterization of inositol phospho-sphingolipid-phospholipase C 1 (Isc1) in Cryptococcus neoformans reveals unique biochemical features.
In this work, we biochemically characterized inositol phosphosphingolipid-phospholipase C (Isc1) from the pathogenic fungus Cryptococcus neoformans. Unlike Isc1 from other fungi and parasites which hydrolyze both fungal complex sphingolipids (IPC-PLC) and mammalian sphingomyelin (SM-PLC), C. neoformans Isc1 only exerts IPC-PLC activity. Genetic mutations thought to regulate substrate recognition in other Isc1 proteins do not restore SM-PLC activity of the cryptococcal enzyme. C. neoformans Isc1 regulates the level of complex sphingolipids and certain species of phytoceramide, especially when fungal cells are exposed to acidic stress. Since growth in acidic environments is required for C. neoformans to cause disease, this study has important implications for understanding of C. neoformans pathogenicity.
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Jennifer
J
Henry
Aimee
A
Guillotte
Chiara
C
Luberto
Maurizio
M
Del Poeta
D002518:Ceramides / Q000378:metabolism*; D003455:Cryptococcus neoformans / Q000201:enzymology* / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D006028:Glycosphingolipids / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*; D013312:Stress, Physiological; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D002518:Ceramides; D005656:Fungal Proteins; D006028:Glycosphingolipids; D050505:Mutant Proteins; D013107:Sphingolipids; C479822:mannosylinositol phosphoylceramide; C068388:mannosylinositolphosphoceramide; D010738:Type C Phospholipases
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