Hyphal Orientation of Candida albicans Is Regulated by a Calcium-Dependent Mechanism

Abstract

SummaryEukaryotic cells from fungal hyphae to neurites that grow by polarized extension must coordinate cell growth and cell orientation to enable them to exhibit growth tropisms and to respond to relevant environmental cues. Such cells generally maintain a tip-high Ca2+ cytoplasmic gradient, which is correlated with their ability to exhibit polarized tip growth and to respond to growth-directing extracellular signals [1–5]. In yeast and other fungi, the polarisome, exocyst, Arp2/3, and Spitzenkörper protein complexes collectively orchestrate tip growth and cell polarity, but it is not clear whether these molecular complexes also regulate cell orientation or whether they are influenced by cytoplasmic Ca2+ gradients. Hyphae of the human pathogenic fungus Candida albicans reorient their growth axis in response to underlying surface topography (thigmotropism) [6] and imposed electric fields (galvanotropism) [7]. The establishment and maintenance of directional growth in relation to these environmental cues was Ca2+ dependent. Tropisms were attenuated in media containing low Ca2+, or calcium-channel blockers, and in mutants where calcium channels or elements of the calcium signaling pathway were deleted. Therefore galvanotropism and thigmotropism may both be mediated by localized Ca2+ influx at sites of polarized growth via Ca2+ channels that are activated by appropriate environmental signals.

Fungal Morphogenesis

“…Thigmotropism is seen when growing hyphae come into contact with a ridge. Instead of continuing through the ridge, hyphae modify their growth direction (Brand et al 2007). This response involves two plasma membrane proteins, Mid1 and Cch1, which are components of the highaffinity calcium uptake system, and Fig.…”

“…This response involves two plasma membrane proteins, Mid1 and Cch1, which are components of the highaffinity calcium uptake system, and Fig. 1, a member of the low-affinity calcium system (Brand et al 2007). The Mid1/Cch1 complex has been suggested to act as a mechanosensitive channel that takes up calcium in response to contact.…”

“…(Image provided by S. Esher and K. Selvig, Duke University.) X. Lin et al Idnurm and Heitman 2005;Brand et al 2007). In contrast, yeasts or yeast-like cells (including conidia, endospores, etc.)…”

Cch1 and Mid1 Are Functionally Required for Vegetative Growth under Low-Calcium Conditions in the Phytopathogenic Ascomycete Botrytis cinerea

“…In G. zeae, the double mutant of both channel proteins exhibited a stronger phenotype than the single mid1 deletion mutant (26), supporting the idea of both dependent and independent roles for Mid1 and Cch1. In B. cinerea, the single and double knockout mutants displayed similar phenotypes under all conditions tested, suggesting that these two proteins act in a complex and have common functions, as also reported for mid1 and cch1 knockout mutants in Candida albicans and S. cerevisiae (21)(22)(23)58). To study a putative interaction between these two proteins in B. cinerea, we used a split ubiquitinbased yeast two-hybrid system (Dualsystems).…”

Deletion of Mid1, a putative stretch-activated calcium channel in Claviceps purpurea, affects vegetative growth, cell wall synthesis and virulence

“…albicans Mid1 forms a complex with the voltagegated Ca 2+ channel Cch1 (Brand et al, 2007); Mid1 is probably activated by membrane stretching and mediates the subsequent opening of the Cch1 channel, thus leading to localized Ca 2+ influx. A reduced growth rate has been observed in mid1, cch1 and the double knockout mutant, whereas the extension rate of hyphae remains unaffected.…”