title: Rsr1 focuses Cdc42 activity at hyphal tips and promotes maintenance of hyphal development in Candida albicans.
abstract: The extremely elongated morphology of fungal hyphae is dependent on the cell's ability to assemble and maintain polarized growth machinery over multiple cell cycles. The different morphologies of the fungus Candida albicans make it an excellent model organism in which to study the spatiotemporal requirements for constitutive polarized growth and the generation of different cell shapes. In C. albicans, deletion of the landmark protein Rsr1 causes defects in morphogenesis that are not predicted from study of the orthologous protein in the related yeast Saccharomyces cerevisiae, thus suggesting that Rsr1 has expanded functions during polarized growth in C. albicans. Here, we show that Rsr1 activity localizes to hyphal tips by the differential localization of the Rsr1 GTPase-activating protein (GAP), Bud2, and guanine nucleotide exchange factor (GEF), Bud5. In addition, we find that Rsr1 is needed to maintain the focused localization of hyphal polarity structures and proteins, including Bem1, a marker of the active GTP-bound form of the Rho GTPase, Cdc42. Further, our results indicate that tip-localized Cdc42 clusters are associated with the cell's ability to express a hyphal transcriptional program and that the ability to generate a focused Cdc42 cluster in early hyphae (germ tubes) is needed to maintain hyphal morphogenesis over time. We propose that in C. albicans, Rsr1 "fine-tunes" the distribution of Cdc42 activity and that self-organizing (Rsr1-independent) mechanisms of polarized growth are not sufficient to generate narrow cell shapes or to provide feedback to the transcriptional program during hyphal morphogenesis.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pulver
authors.forename: Timothy
authors.initials: T
authors.lastname: Heisel
authors.forename: Sara
authors.initials: S
authors.lastname: Gonia
authors.forename: Robert
authors.initials: R
authors.lastname: Robins
authors.forename: Jennifer
authors.initials: J
authors.lastname: Norton
authors.forename: Paula
authors.initials: P
authors.lastname: Haynes
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Gale
mesh_terms: D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D025301:Hyphae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: C466987:BEM1 protein, Candida albicans; C083102:BUD2 protein, S cerevisiae; C091391:BUD5 protein, S cerevisiae; D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D029701:Saccharomyces cerevisiae Proteins; C084013:RSR1 protein, S cerevisiae; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020691:rab GTP-Binding Proteins