Npc1 is involved in sterol trafficking in the filamentous fungus Fusarium graminearum

Andrew Breakspear, Matias Pasquali, Karen Broz, Yanhong Dong, H. Corby Kistler

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The ortholog of the human gene NPC1 was identified in the plant pathogenic, filamentous fungus Fusarium graminearum by shared amino acid sequence, protein domain structure and cellular localization of the mature fungal protein. The Fusarium Npc1 gene shares 34% amino acid sequence identity and 51% similarity to the human gene, has similar domain structure and is constitutively expressed, although up-regulated in ungerminated macroconidia and ascospores. GFP-tagged Npc1p localizes to the fungal vacuolar membrane. Cultures derived from a Δ. npc1 mutant strain contain significantly more ergosterol than cultures of the wildtype. Staining with the fluorescent, sterol binding dye filipin, shows that ergosterol accumulates in vacuoles of the Δ. npc1 mutant but not the wildtype strain. The Δ. npc1 mutant has a temperature dependent reduction in growth and greater sensitivity to the ergosterol synthesis inhibiting fungicide tebuconazole compared with the wildtype strain or the mutant complemented with wildtype Npc1. The mutant also is significantly reduced in pathogenicity to wheat. Our results are consistent with the interpretation that Npc1p is important for normal transport of ergosterol from the vacuole and is essential for proper membrane function under particular environmental conditions.

Original languageEnglish (US)
Pages (from-to)725-730
Number of pages6
JournalFungal Genetics and Biology
Volume48
Issue number7
DOIs
StatePublished - Jul 2011

Bibliographical note

Funding Information:
This project was supported by the National Research Initiative Competitive Grants Program Grant number 2010-65108-20642 from the USDA National Institute of Food and Agriculture.

Keywords

  • Azole antifungals
  • Ergosterol
  • Fungicides
  • Niemann-Pick type C disease

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