The Claudin Family Protein FigA Mediates Ca Homeostasis in Response to Extracellular Stimuli in and .

The claudin family protein Fig1 is a unique fungal protein that is involved in pheromone-induced calcium influx and membrane fusion during the mating of and . Whether and how Fig1 regulates Ca homeostasis in response to extracellular stimuli is poorly understood. Previously, we found FigA, a homolog of Fig1 in , similar to the high-affinity calcium uptake system, is required for normal growth under low-Ca minimal medium. In this study, using the calcium-sensitive photoprotein aequorin to monitor cytosolic free calcium concentration ([Ca]) in living cells, we found that the FigA dysfunction decreases the transient [Ca] induced by a high extracellular calcium stress. Furthermore, FigA acts synergistically with CchA (a high-affinity Ca channel) to coordinate cytoplasmic Ca influx in response to an extracellular Ca stimulus. Moreover, FigA mediates ER stress-induced transient [Ca] in the presence or absence of extracellular calcium. Most importantly, these [Ca] responses mediated by FigA are closely related to its conserved claudin superfamily motif, which is also required for hyphal growth and asexual development in . Finally, the function of FigA in , the most common airborne human fungal pathogen was studied. The result showed that the two FigA homologous in and have a large degree of functional homology not only in asexual development but also in regulating transient [Ca]. Our study expands the knowledge of claudin family protein FigA in Ca homeostasis in response to extracellular stimuli.