A functional analysis of the Candida albicans homolog of Saccharomyces cerevisiae VPS4

Samuel A. Lee, Jason Jones, Zachary Khalique, John Kot, Mercedes Alba, Stella Bernardo, Alfica Seghal, Brian Wong

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

To investigate the role of the prevacuolar secretion pathway in the trafficking of vacuolar proteins in Candida albicans, the C. albicans homolog of the Saccharomyces cerevisiae vacuolar protein sorting gene VPS4 was cloned and analyzed. Candida albicans VPS4 encodes a deduced AAA-type ATPase that is 75.6% similar to S. cerevisiae Vps4p, and plasmids bearing C. albicans VPS4 complemented the abnormal vacuolar morphology and carboxypeptidase missorting in S. cerevisiae vps4 null mutants. Candida albicans vps4Δ null mutants displayed a characteristic class E vacuolar morphology and multilamellar structures consistent with an aberrant prevacuolar compartment. The C. albicans vps4Δ mutant degraded more extracellular bovine serum albumin than did wild-type strains, which implied that this mutant secreted more extracellular protease activity. These phenotypes were complemented when a wild-type copy of VPS4 was reintroduced into its proper locus. Using a series of protease inhibitors, the origin of this extracellular protease activity was identified as a serine protease, and genetic analyses using a C. albicans vps4Δ prc1Δ mutant identified this missorted vacuolar protease as carboxypeptidase Y. Unexpectedly, C. albicans Sap2p was not detected in culture supernatants of the vps4Δ mutants. These results indicate that C. albicans VPS4 is required for vacuolar biogenesis and proper sorting of vacuolar proteins.

Original languageEnglish (US)
Pages (from-to)973-985
Number of pages13
JournalFEMS Yeast Research
Volume7
Issue number6
DOIs
StatePublished - Sep 2007

Keywords

  • Candida albicans
  • Protein secretion
  • Secreted aspartyl proteases
  • VPS
  • Vacuole

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology

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