title: Inositol phosphosphingolipid phospholipase C1 regulates plasma membrane ATPase (Pma1) stability in Cryptococcus neoformans.
abstract: Cryptococcus neoformans is a facultative intracellular pathogen, which can replicate in the acidic environment inside phagolysosomes. Deletion of the enzyme inositol-phosphosphingolipid-phospholipase-C (Isc1) makes C. neoformans hypersensitive to acidic pH likely by inhibiting the function of the proton pump, plasma membrane ATPase (Pma1). In this work, we examined the role of Isc1 on Pma1 transport and oligomerization. Our studies showed that Isc1 deletion did not affect Pma1 synthesis or transport, but significantly inhibited Pma1 oligomerization. Interestingly, Pma1 oligomerization could be restored by supplementing the medium with phytoceramide. These results offer insight into the mechanism of intracellular survival of C. neoformans.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY 11794, USA.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Farnoud
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY 11794, USA.
authors.forename: Visesato
authors.initials: V
authors.lastname: Mor
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY 11794, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY 11794, USA. Electronic address: maurizio.delpoeta@stonybrook.edu.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Del Poeta
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D002518:Ceramides / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D004795:Enzyme Stability; D017353:Gene Deletion; D042541:Intracellular Space / Q000382:microbiology; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000187:drug effects; D010738:Type C Phospholipases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D002518:Ceramides; D010738:Type C Phospholipases; D000251:Adenosine Triphosphatases
keywords: Cryptococcus neoformans; Inositiol phosphosphingolipid phospholipase C (Isc1); Plasma membrane; Plasma membrane ATPase (Pma1); Sphingolipid