Abnormal sterols disrupt cellular functions through yet unclear mechanisms. In Saccharomyces cerevisiae, accumulation of Δ8-sterols, the same type of sterols observed in patients of Conradi–Hünermann–Happle syndrome or in fungi after amine fungicide treatment, leads to cell wall weakness. We have studied the influence of Δ8-sterols on the activity of glucan synthase I, the protein synthetizing the main polymer in fungal cell walls, its regulation by the Cell Wall Integrity (CWI) pathway, and its transport from the endoplasmic reticulum to the plasma membrane. We ascertained that the catalytic characteristics were mostly unaffected by the presence of abnormal sterols but the enzyme was partially retained in the endoplasmic reticulum, leading to glucan deficit at the cell wall. Furthermore, we observed that glucan synthase I traveled through an unconventional exocytic route to the plasma membrane that is associated with low density intracellular membranes. Also, we found out that the CWI pathway remained inactive despite low glucan levels at the cell wall. Taken together, these data suggest that Δ8-sterols affect cell walls by inhibiting unconventional secretion of proteins leading to retention and degradation of glucan synthase I, while the compensatory CWI pathway is unable to activate. These results could be instrumental to understand defects of bone development in cholesterol biosynthesis disorders and fungicide mechanisms of action.
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December 2020
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The cover image shows the ternary complex structure of pol? incorporating dCTP* opposite templating xanthine. In this issue Jung and colleagues (pp. 4797–4810) demonstrate the solved structure of human DNA polymerase η (ploη) catalyzing across xanthine and hypoxanthine. Image courtesy of Seongmin Lee.
Research Article|
December 18 2020
Abnormal sterol-induced cell wall glucan deficiency in yeast is due to impaired glucan synthase transport to the plasma membrane
L. Roxana Gutierrez-Armijos;
L. Roxana Gutierrez-Armijos
1Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (SP), Brazil
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Rodrigo A. C. Sussmann;
Rodrigo A. C. Sussmann
1Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (SP), Brazil
2Centro de Formação em Ciências Ambientais, Universidade Federal do Sul da Bahia, Porto Seguro (BA), Brazil
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Ariel M. Silber
;
Ariel M. Silber
1Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (SP), Brazil
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Mauro Cortez
;
Mauro Cortez
Validation, Methodology, Writing - review & editing
1Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (SP), Brazil
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Agustín Hernández
1Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (SP), Brazil
3Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos (SP), Brazil
Correspondence: Agustín Hernández (agustin.hernandez@ufscar.br)
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Publisher: Portland Press Ltd
Received:
August 18 2020
Revision Received:
October 21 2020
Accepted:
October 22 2020
Accepted Manuscript online:
October 23 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (24): 4729–4744.
Article history
Received:
August 18 2020
Revision Received:
October 21 2020
Accepted:
October 22 2020
Accepted Manuscript online:
October 23 2020
Citation
L. Roxana Gutierrez-Armijos, Rodrigo A. C. Sussmann, Ariel M. Silber, Mauro Cortez, Agustín Hernández; Abnormal sterol-induced cell wall glucan deficiency in yeast is due to impaired glucan synthase transport to the plasma membrane. Biochem J 23 December 2020; 477 (24): 4729–4744. doi: https://doi.org/10.1042/BCJ20200663
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