ArticleThe Journal of biological chemistry2010
Cch1 restores intracellular Ca2+ in fungal cells during endoplasmic reticulum stress.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Do Magnesium Ions Have Similar Effects as Calcium Ions on Resting Membrane Potential?Membranes · 2026Article
- Calcium transport systems as virulence determinants: Mechanistic insights into fungal pathogenicity and antifungal resistance.Virulence · 2025Review
- NALCN/Cch1 channelosome subunits originated in early eukaryotes.The Journal of general physiology · 2025Article
- Impairing the interaction between Erg11 and cytochrome P450 reductase Ncp1 enhances azoles' antifungal activities.Nature communications · 2025Article
- Calcium Signaling Is a Universal Carbon Source Signal Transducer and Effects an Ionic Memory of Past Carbon Sources.International journal of molecular sciences · 2025Article
- MoCbp7, a Novel Calcineurin B Subunit-Binding Protein, Is Involved in the Calcium Signaling Pathway and Regulates Fungal Development, Virulence, and ER Homeostasis inInternational journal of molecular sciences · 2023Article
- Calcium Ion Channels inJournal of fungi (Basel, Switzerland) · 2023Review
- CaJournal of fungi (Basel, Switzerland) · 2022Article
- Cation Transporters ofBiomolecules · 2021Review
- Highly conserved extracellular residues mediate interactions between pore-forming and regulatory subunits of the yeast CaThe Journal of biological chemistry · 2020Article
- Calcium Transport Proteins in Fungi: The Phylogenetic Diversity of Their Relevance for Growth, Virulence, and Stress Resistance.Frontiers in microbiology · 2019Review
- Diversity and evolution of four-domain voltage-gated cation channels of eukaryotes and their ancestral functional determinants.Scientific reports · 2018Article
- The Claudin Family Protein FigA Mediates CaFrontiers in microbiology · 2018Article
- Article
- Post-translational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family.The Journal of biological chemistry · 2017Article
- The Lectin Chaperone Calnexin Is Involved in the Endoplasmic Reticulum Stress Response by Regulating CaApplied and environmental microbiology · 2017Article
- Article
- Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae.Scientific reports · 2016Article
- Palmitoylation of the Cysteine Residue in the DHHC Motif of a Palmitoyl Transferase Mediates Ca2+ Homeostasis in Aspergillus.PLoS genetics · 2016Article
- The Cch1-Mid1 High-Affinity Calcium Channel Contributes to the Virulence of Cryptococcus neoformans by Mitigating Oxidative Stress.Eukaryotic cell · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pathogens endure and proliferate during infection by exquisitely coping with the many stresses imposed by the host to prevent pathogen survival. Recent evidence has shown that fungal pathogens and yeast respond to insults to the endoplasmic reticulum (ER) by initiating Ca(2+) influx across their plasma membrane. Although the high affinity Ca(2+) channel, Cch1, and its subunit Mid1, have been suggested as the protein complex responsible for mediating Ca(2+) influx, a direct demonstration of the gating mechanism of the Cch1 channel remains elusive. In this first mechanistic study of Cch1 channel activity we show that the Cch1 channel from the model human fungal pathogen, Cryptococcus neoformans, is directly activated by the depletion of intracellular Ca(2+) stores. Electrophysiological analysis revealed that agents that enable ER Ca(2+) store depletion promote the development of whole cell inward Ca(2+) currents through Cch1 that are effectively blocked by La(3+) and dependent on the presence of Mid1. Cch1 is permeable to both Ca(2+) and Ba(2+); however, unexpectedly, in contrast to Ca(2+) currents, Ba(2+) currents are steeply voltage-dependent. Cch1 maintains a strong Ca(2+) selectivity even in the presence of high concentrations of monovalent ions. Single channel analysis indicated that Cch1 channel conductance is small, similar to that reported for the Ca(2+) current I(CRAC). This study demonstrates that Cch1 functions as a store-operated Ca(2+)-selective channel that is gated by intracellular Ca(2+) depletion. The inability of cryptococcal cells that lacked the Cch1-Mid1 channel to survive ER stress suggests that Cch1 and its co-regulator, Mid1, are critical players in the restoration of Ca(2+) homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.