Hyphal Elongation Is Regulated Independently of Cell Cycle inCandida albicans

Abstract

The mechanism for apical growth during hyphal morphogenesis in Candida albicans is unknown. Studies from Saccharomyces cerevisiae indicate that cell morphogenesis may involve cell cycle regulation by cyclin-dependent kinase. To examine whether this is the mechanism for hyphal morphogenesis, the temporal appearance of different spindle pole body and spindle structures, the cell cycle-regulated rearrangements of the actin cytoskeleton, and the phosphorylation state of the conserved Tyr19 of Cdc28 during the cell cycle were compared and found to be similar between yeast and serum-induced hyphal apical cells. These data suggest that hyphal elongation is not mediated by altering cell cycle progression or through phosphorylation of Tyr19 of Cdc28. We have also shown that germ tubes can evaginate before spindle pole body duplication, chitin ring formation, and DNA replication. Similarly, tip-associated actin polarization in each hypha occurs before the events of the G 1 /S transition and persists throughout the cell cycle, whereas cell cycle-regulated actin assemblies come and go. We have also shown that cells in phases other than G 1 can be induced to form hyphae. Hyphae induced from G 1 cells have no constrictions, and the first chitin ring is positioned in the germ tube at various distances from the base. Hyphae induced from budded cells have a constriction and a chitin ring at the bud neck, beyond which the hyphae continue to elongate with no further constrictions. Our data suggest that hyphal elongation and cell cycle morphogenesis programs are uncoupled, and each contributes to different aspects of cell morphogenesis. INTRODUCTIONCandida albicans is a polymorphic fungal pathogen that undergoes reversible morphogenetic transitions among budding, pseudohyphal, and hyphal growth forms (Odds, 1985). Its ability to switch between yeast and hyphal growth forms is directly related to its virulence, because mutants defective in hyphal growth are less virulent in mouse models than are their wild-type counterparts (Leberer et al., 1997;Lo et al., 1997;Gale et al., 1998). Hyphae may be suited to breach barriers in the host, whereas the yeast form is more easily disseminated within the host. Therefore, understanding the mechanisms for this morphogenetic switch should provide insight into the pathogenicity of this fungus.During hyphal growth in C. albicans, cell surface expansion is restricted to a small region at the hyphal tip. This apical growth zone is active during the entire hyphal growth period (Staebell and Soll, 1985). In contrast, yeast-form cells expand from a small area in a mostly apical manner only at the initial stage of budding. When the bud has reached a critical size, apical growth shuts down and general (isotropic) expansion takes place (Staebell and Soll, 1985). The localization of the actin cytoskeleton in yeast and hyphal cells reflects these differences in morphogenesis. Polarization of the actin cytoskeleton to the hyphal tip is observed in all hyphal cells (Anderson and Soll, 1986). However, in yeast-...

Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation

“…3D). Hyphae initiated from unbudded G 1 cells gave rise to germ tubes without constriction at the base of germ tube, whereas hyphae initiated from budded cells (non-G 1 cells) generated elongated buds with a constriction (25). Our results suggest that release from farnesol inhibition promotes Nrg1 degradation through transient activation of SOK1 expression for hyphal initiation.…”

Characterization and Functional Analysis of the Siderophore-Iron Transporter CaArn1p in Candida albicans

“…These two organisms are well known to differ in the number of ARN genes, specificity for siderophores, and ability in siderophore production. A similar situation is the ability of C. albicans (but not S. cerevisiae) to shift a dynamic cell cycle-dependent distribution of a pool of actin toward a persistent localization at the hyphal tips when cells switch growth from the yeast form to the filamentous form (48). Then, what is the relationship between the CaArn1p molecules in the two locations?…”

Depletion of a Polo-like Kinase inCandida albicansActivates Cyclase-dependent Hyphal-like Growth

“…The GFP-tagged CaCDC5-regulated strain (CB112), however, was somewhat more sensitive to the absence of CaCdc5p than strain CB104, as the filaments were shorter in length at the various time points. The majority of cells from strain CB112 depleted of CaCdc5p for 3 h were elongated or large doublets ( Figure 4A; Table 5) and contained spindles in the form of distinct spots or two spots side by side, corresponding to unseparated spindle pole bodies or very short spindles in S-G2 phases of the cell cycle (Barton and Gull, 1988;Hazan et al, 2002). Despite the elongated and large doublet morphology of cells at 3 h, only 2.2% of the population contained an extended mitotic spindle.…”

“…In filamentous and dimorphic fungi, the connection between cell cycle factors and true hyphal growth is less clear. Hyphae continue to grow whether their apical-most nuclei are in interphase or mitosis (Kron and Gow, 1995), and it was recently demonstrated that the duration of cell cycle stages was similar in yeast, germlings, and apical hyphal cells of C. albicans (Hazan et al, 2002). However, the coordination between nuclear localization, division, and septation with the initiation and maintenance of hyphal growth in Candida requires a relationship between aspects of the cell cycle and hyphal growth.…”