title: Candida albicans Vrp1 is required for polarized morphogenesis and interacts with Wal1 and Myo5.
abstract: Recently, a link between endocytosis and hyphal morphogenesis has been identified in Candida albicans via the Wiskott-Aldrich syndrome gene homologue WAL1. To get a more detailed mechanistic understanding of this link we have investigated a potentially conserved interaction between Wal1 and the C. albicans WASP-interacting protein (WIP) homologue encoded by VRP1. Deletion of both alleles of VRP1 results in strong hyphal growth defects under serum inducing conditions but filamentation can be observed on Spider medium. Mutant vrp1 cells show a delay in endocytosis - measured as the uptake and delivery of the lipophilic dye FM4-64 into small endocytic vesicles - compared to the wild-type. Vacuolar morphology was found to be fragmented in a subset of cells and the cortical actin cytoskeleton was depolarized in vrp1 daughter cells. The morphology of the vrp1 null mutant could be complemented by reintegration of the wild-type VRP1 gene at the BUD3 locus. Using the yeast two-hybrid system we could demonstrate an interaction between the C-terminal part of Vrp1 and the N-terminal part of Wal1, which contains the WH1 domain. Furthermore, we found that Myo5 has several potential interaction sites on Vrp1. This suggests that a Wal1-Vrp1-Myo5 complex plays an important role in endocytosis and the polarized localization of the cortical actin cytoskeleton to promote polarized hyphal growth in C. albicans.
authors.affiliation: Junior Research Group: Growth Control of Fungal Pathogens, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute and Department of Microbiology, Friedrich Schiller University, D-07745 Jena, Germany.|Carlsberg Laboratory, Yeast Biology, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
authors.forename: Nicole
authors.initials: N
authors.lastname: Borth
authors.affiliation: Junior Research Group: Growth Control of Fungal Pathogens, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute and Department of Microbiology, Friedrich Schiller University, D-07745 Jena, Germany.|Carlsberg Laboratory, Yeast Biology, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
authors.forename: Andrea
authors.initials: A
authors.lastname: Walther
authors.affiliation: Carlsberg Laboratory, Yeast Biology, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
authors.forename: Patrick
authors.initials: P
authors.lastname: Reijnst
authors.affiliation: Carlsberg Laboratory, Yeast Biology, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
authors.forename: Sigyn
authors.initials: S
authors.lastname: Jorde
authors.affiliation: Junior Research Group: Growth Control of Fungal Pathogens, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute and Department of Microbiology, Friedrich Schiller University, D-07745 Jena, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schaub
authors.affiliation: Junior Research Group: Growth Control of Fungal Pathogens, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute and Department of Microbiology, Friedrich Schiller University, D-07745 Jena, Germany.|Carlsberg Laboratory, Yeast Biology, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wendland
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D002176:Candida albicans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D025301:Hyphae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D024701:Myosin Type V / Q000378:metabolism; D025941:Protein Interaction Mapping; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D014617:Vacuoles / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism
chemical_list: D000199:Actins; D005656:Fungal Proteins; D008840:Microfilament Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; D024701:Myosin Type V