Cited by 191Fungal and yeast genetics researchIon channel regulation and functionIon Channels and Receptors

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A Homolog of Mammalian, Voltage-Gated Calcium Channels Mediates Yeast Pheromone-Stimulated Ca 2+ Uptake and Exacerbates the cdc1 (Ts) Growth Defect

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Paidhungat, Madan, Garrett, Stephen·1997·Molecular and Cellular Biology

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Abstract

Previous studies attributed the yeast (Saccharomyces cerevisiae) cdc1(Ts) growth defect to loss of an Mn2+-dependent function. In this report we show that cdc1(Ts) temperature-sensitive growth is also associated with an increase in cytosolic Ca2+. We identified two recessive suppressors of the cdc1(Ts) temperature-sensitive growth which block Ca2+ uptake and accumulation, suggesting that cytosolic Ca2+ exacerbates or is responsible for the cdc1(Ts) growth defect. One of the cdc1(Ts) suppressors is identical to a gene, MID1, recently implicated in mating pheromone-stimulated Ca2+ uptake. The gene (CCH1) corresponding to the second suppressor encodes a protein that bears significant sequence similarity to the pore-forming subunit (alpha1) of plasma membrane, voltage-gated Ca2+ channels from higher eukaryotes. Strains lacking Mid1 or Cch1 protein exhibit a defect in pheromone-induced Ca2+ uptake and consequently lose viability upon mating arrest. The mid1delta and cch1delta mutants also display reduced tolerance to monovalent cations such as Li+, suggesting a role for Ca2+ uptake in the calcineurin-dependent ion stress response. Finally, mid1delta cch1delta double mutants are, by both physiological and genetic criteria, identical to single mutants. These and other results suggest Mid1 and Cch1 are components of a yeast Ca2+ channel that may mediate Ca2+ uptake in response to mating pheromone, salt stress, and Mn2+ depletion.

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Directed evolution for cell separation in natural isolates of budding yeast reveals selection to deactivate AMN1 and the Rim101 pathway in haploids and selection in favor of Hawthorne's deletion in diploids
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“CCH1 is homologous to human CACNA1A (Paidhungat and Garrett 1997) and encodes the voltage-gated calcium channel sub-unit α 1A. Variants of CACNA1A are implicated in several neurological diseases (Rajakulendran et al. 2012).”
Enhanced Ethanol Production of Saccharomyces cerevisiae Induced by Cold Plasma at Atmospheric Air Pressure
Dong, X.-Y. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.78019 · Cited by 3
Does light taste salty?
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The effect of azalomycin F on Ca2+ homeostasis in Trichoderma viride and Saccharomyces cerevisiae.
Šimkovič, M., Lakatoš, B., Fi, T., Muto, S., & Varečka, Ĺ. (2001) · PubMed · Cited by 3
Genomic Data Mining Reveals Abundant Uncharacterized Transporters in Coccidioides immitis and Coccidioides posadasii
Cai, H., Zhang, H., Guo, D. H., Wang, Y., & Gu, J. (2022) · Journal of Fungi · doi:10.3390/jof8101064 · Cited by 2
High-Affinity Plasma Membrane Ca2+ Channel Cch1 Modulates Adaptation to Sodium Dodecyl Sulfate-Triggered Rise in Cytosolic Ca2+ Concentration in Ogataea parapolymorpha
Kulakova, M. V., Pakhomova, M., Bidiuk, V. A., Ershov, A., Alexandrov, A. I., & Agaphonov, M. O. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111450 · Cited by 2
The Ycx1 protein encoded by the yeast YDL206W gene plays a role in calcium and calcineurin signaling
Lee, G. M., Weng, F., Cranley, J., Rajasekhar, A., Stoeckel, M., Kane, T., Tisi, R., & Wang, Y. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104647 · Cited by 2
“…in ﬂ ux of calcium through the plasma membrane is mainly mediated by the high-af ﬁ nity calcium transporter, a protein complex composed of Mid1 (18), Cch1 (18), and Ecm7 (19), and the release of calcium from its major storage site vacuole is achieved via Yvc1, a vacuolar cation channel (20,…”
Background
Phe356 in the yeast Ca2+ channel component Mid1 is a key residue for viability after exposure to α-factor
Tada, T., Ohmori, M., & Iida, H. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.166 · Cited by 2
Comparative transcriptome analysis of the calcium signaling and expression analysis of sodium/calcium exchanger in Aspergillus cristatus
Ren, X., Wang, Y., Liu, Y., Tan, Y., Ren, C., Ge, Y., & Liu, Z. (2017) · Journal of Basic Microbiology · doi:10.1002/jobm.201700277 · Cited by 2
Yeast as a Molecular Genetic System for Improvement of Plant Salt Tolerance
Matsumoto, T. K., Bressan, R. A., Hasegawa, P. M., & Pardo, J. M. (2002) · Plant breeding reviews · doi:10.1002/9780470650202.ch8 · Cited by 2
The Genetic Profiles of TIF1 and TIF2 Duplicate Genes
Venturi, V. (2012) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.16999348.v1 · Cited by 1
Calcium Channel Mutations and Associated Diseases
Mori, Y., Itsukaichi, Y., Nishida, M., & Oka, H. (2004) · Springer eBooks · doi:10.1007/978-1-4419-9254-3_9 · Cited by 1
Calcium homeostasis plays important roles in the internalization and activities of the small synthetic antifungal peptide PAF26
Alexander, A. J. T., Muñoz, A., Marcos, J. F., & Read, N. D. (2020) · Molecular Microbiology · doi:10.1111/mmi.14532 · Cited by 1
“…Sachs, 1989; Bertl and Slayman, 1990; Diamond et al., 1991; Antebi and Fink, 1992; Iida et al., 1994; Lapinskas et al., 1995; Levina et al., 1995; Paidhungat and Garrett, 1997; Erdman et al., 1998; Kanzaki, 1999; Benito et al., 2000; Locke et al., 2000; Muller et al., 2001; Palmer et al., 2001;…”
Background
Thigmo Responses: The Fungal Sense of Touch
Almeida, M. C., & Brand, A. (2017) · ASM Press eBooks · doi:10.1128/9781555819583.ch22 · Cited by 2
Signalling towards cell wall synthesis in budding yeast.
Raclavský, V. (1998) · PubMed · Cited by 1
Voltage‐Gated Ion Channels
Fay, A. J., Haddick, P. C. G., & Jan, L. Y. (2007) · doi:10.1002/9780470101001.hcn014 · Cited by 1
Paracoccidioides brasiliensis during Mycelium-to-Yeast Dimorphism of Morphogenesis and Calcium Homeostasis Evidence for the Role of Calcineurin in
Ovalle, R., Nóbrega, M. P., & de Campos, C. B. L. (2014)
Involvement of the putative Ca 2+ -permeable mechanosensitive channels, NtMCA1 and NtMCA2, in Ca 2+ uptake, Ca 2+ -dependent cell proliferation and mechanical stress-induced gene expression in tobacco (Nicotiana tabacum) BY-2 cells Takamitsu KurusuTakuya YamanakaMasataka NakanoAkiko TakiguchiYoko Ogasawara • Teruyuki HayashiKazuko IidaShigeru HanamataKazuo ShinozakiHidetoshi IidaKazuyuki Kuchitsu
Nakano, M., Hayashi, T., Iida, K., & Shinozaki, K. (2012)
Functional characterization of cell wall damage response genes in Arabidopsis thaliana
Carraca, L. P. V. (2012) · Spiral (Imperial College London) · doi:10.25560/11644
Characterization of the Plant Cell Wall Response to Isoxaben induced Cell Wall Damage
Kjær, L. (2011) · Spiral (Imperial College London) · doi:10.25560/9630
“Additionally mechanical stimuli have been found to cause elevated Ca2+, which also functions as an osmotic stress signal initiated by MID2/ (CCH1) in S. cerevesiae (Paidhungat and Garrett, 1997, Green et al., 2003, Knight et al., 1992, Haley, 1995, Ono et al., 1994).”
Background
Universidade Federal do Rio Grande do Sul Centro de Biotecnologia do Rio Grande do Sul Programa de Pós-Graduação em Biologia Celular e Molecular Novos aspectos da desintoxicação de cádmio em Saccharomyces cerevisiae: regulação do transportador Ycf1p durante o metabolismo respiratório e contribuição de transportadores de cálcio.
Alegre, P. (2009)
Endosomal Trafficking as a Determinant of Antifungal Tolerance in the Pathogenic Fungus Candida albicans
Luna, A. (2016) · doi:10.21007/etd.cghs.2016.0417
“Entry of extracellular Ca2+ into the fungal cells depends on several Ca2+ channels located at the plasma membrane including the voltage-gated calcium channel formed by Mid1p/Cch1p (161, 240), a high-affinity Ca2+ influx system.”
Background
Calcium Signaling Is a Universal Carbon Source Signal Transducer and Effects an Ionic Memory of Past Carbon Sources
Simpson-Lavy, K. J., & Kupiec, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052198
“Calcium ions are imported into the cyto-plasm from the external medium by the Mid1-Cch1 channel [23].”
Regulation of Yeast Cytokinesis by Calcium
Chen, Q. (2025) · Journal of Fungi · doi:10.3390/jof11040278
Inactivation of the High-Affinity Ca2+ Uptake System Delays the Amiodarone-Induced Ca2+ Influx in Yeast Ogataea parapolymorpha
Kulakova, M. V., Pakhomova, M., Bidiuk, V. A., & Agaphonov, M. O. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262311386
“While the Cch1 predicted topology [28] and its homology to mammalian voltage-gated Ca 2+ channels [8] indicate that it is the channel-forming subunit, the exact role of Mid1 in the complex remains unclear.”
Calcium transport and signaling
Ramakrishnan, S., & Docampo, R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-811114-7.00003-7
Identification de protéines impliquées dans le devenir de l'uranium dans la plante Arabidopsis thaliana et la levure Saccharomyces cerevisiae.
Revel, B. (2021) · doi:10.70675/32d9a60az3137z4d7az8942z7f88893260fa
The plant cell wall integrity sensing mechanism
Tsang, D. L. (2013) · Research Explorer (The University of Manchester)
Développement de l’activité rythmique chez l’embryon du poisson-zébré
Ryan, J. (2010) · doi:10.71781/28955
The role of calcium in Saccharomyces sp. response to ethanol stress
Duarte, S. O. D. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)

Authors: Paidhungat, M., & Garrett, S.
Affiliations: Duke University (US)
ORCID: Garrett, Stephen
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1997-11
Volume: 17
Issue: 11
Pages: 6339-6347
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.17.11.6339
PMC: PMC232485
OpenAlex: W2162829341
Cited by: 191
References: 40
Citations by year: 2026: 1 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 11 · 2016: 9 · 2015: 6 · 2014: 8 · 2013: 8 · 2012: 12
FWCI: 2.02
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: voltage-gated calcium channels, calcium uptake, MID1, mating pheromone signaling, intracellular calcium, lithium tolerance, manganese depletion, salt stress, Saccharomyces cerevisiae
MeSH terms: Amino Acid Sequence, Biological Transport, Calcium, Fungal Proteins, Membrane Glycoproteins, Molecular Sequence Data, Mutation, Pheromones, Saccharomyces cerevisiae, Suppression, Genetic, Calcium Channels, Ion Channel Gating, Gene Expression, Sequence Homology, Amino Acid, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins

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A Homolog of Mammalian, Voltage-Gated Calcium Channels Mediates Yeast Pheromone-Stimulated Ca 2+ Uptake and Exacerbates the cdc1 (Ts) Growth Defect

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