Cch1 Restores Intracellular Ca2+ in Fungal Cells during Endoplasmic Reticulum Stress

Activity of the Calcium Channel Pore Cch1 Is Dependent on a Modulatory Region of the Subunit Mid1 in Cryptococcus neoformans

“…The survival of C. neoforomans under conditions of ER stress was dependent on the expression of CMC, further indicating that Cch1 and its partner Mid1 play a critical role in the restoration of Ca 2ϩ homeostasis (2). Similarly, yeast (Saccharomyces cerevisiae) survival under conditions of ER stress is supported by an active CMC that likely promotes Ca 2ϩ influx during secretory Ca 2ϩ depletion, consistent with the electrophysiological evidence (5,19,20).…”

“…This notion was supported by evidence from recordings of inward Ca 2ϩ currents that were specifically activated upon the depletion of intracellular ER Ca 2ϩ stores with 1,2-bis(2-aminophenoxy)ethane-N,N,N=,N=-tetraacetic acid, cesium salt (BAPTA-AM; a Ca 2ϩ chelator), or thapsigargin (inhibitor of the SERCA Ca 2ϩ -ATPase) (2). Cch1 was also found to be highly permeable with respect to to both Ca 2ϩ and Ba 2ϩ ions, while La 3ϩ specifically blocked Cch1-mediated Ca 2ϩ currents (2). Ca 2ϩ movement through Cch1 was not voltage dependent, suggesting that CMC is not gated by voltage.…”

“…The recent electrophysiological characterization of CMC revealed that the channel is gated by the depletion of intracellular ER Ca 2ϩ stores, indicating that CMC functions primarily to replenish these stores and reestablish Ca 2ϩ homeostasis (2). This notion was supported by evidence from recordings of inward Ca 2ϩ currents that were specifically activated upon the depletion of intracellular ER Ca 2ϩ stores with 1,2-bis(2-aminophenoxy)ethane-N,N,N=,N=-tetraacetic acid, cesium salt (BAPTA-AM; a Ca 2ϩ chelator), or thapsigargin (inhibitor of the SERCA Ca 2ϩ -ATPase) (2).…”

“…ryptococcus neoformans and other fungi express the Cch1-Mid1 channel (CMC channel) in their plasma membrane (1)(2)(3)(4)(5)(6)(7). C. neoformans is a fungal pathogen that causes life-threatening disease primarily in patients with a compromised immune system (8,9).…”

Redox regulation of the yeast voltage-gated Ca2+ channel homolog Cch1p by glutathionylation of specific cysteine residues

“…Although Cch1p shows significant sequence and structural homology to VGCCs, Ca 2+ movement through Cch1p is not voltage dependent (Martin et al, 2011). Studies on Cch1p have revealed that it responds to different stimuli that include a sudden increase in pH (Viladevall et al, 2004), exposure to mating pheromones (Iida et al, 1994;Muller et al, 2001), store-operated stress (D'hooge et al, 2015;Locke et al, 2000), endoplasmic reticulum (ER) stress (Hong et al, 2010;Locke et al, 2000) and oxidative stress (Popa et al, 2010).…”