Cargando…

LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles

Lam proteins transport sterols between the membranes of different cellular compartments. In Saccharomyces cerevisiae, the LAM gene family consists of three pairs of paralogs. Because the function of paralogous genes can be redundant, the phenotypes of only a small number of LAM gene deletions have b...

Descripción completa

Detalles Bibliográficos
Autores principales: Sokolov, Svyatoslav S., Vorobeva, Margarita A., Smirnova, Alexandra I., Smirnova, Ekaterina A., Trushina, Nataliya I., Galkina, Kseniia V., Severin, Fedor F., Knorre, Dmitry A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997477/
https://www.ncbi.nlm.nih.gov/pubmed/32047490
http://dx.doi.org/10.3389/fmicb.2020.00038
_version_ 1783493707501142016
author Sokolov, Svyatoslav S.
Vorobeva, Margarita A.
Smirnova, Alexandra I.
Smirnova, Ekaterina A.
Trushina, Nataliya I.
Galkina, Kseniia V.
Severin, Fedor F.
Knorre, Dmitry A.
author_facet Sokolov, Svyatoslav S.
Vorobeva, Margarita A.
Smirnova, Alexandra I.
Smirnova, Ekaterina A.
Trushina, Nataliya I.
Galkina, Kseniia V.
Severin, Fedor F.
Knorre, Dmitry A.
author_sort Sokolov, Svyatoslav S.
collection PubMed
description Lam proteins transport sterols between the membranes of different cellular compartments. In Saccharomyces cerevisiae, the LAM gene family consists of three pairs of paralogs. Because the function of paralogous genes can be redundant, the phenotypes of only a small number of LAM gene deletions have been reported; thus, the role of these genes in yeast physiology is still unclear. Here, we surveyed the phenotypes of double and quadruple deletants of paralogous LAM2(YSP2)/LAM4 and LAM1(YSP1)/LAM3(SIP3) genes that encode proteins localized in the junctions of the plasma membrane and endoplasmic reticulum. The quadruple deletant showed increased sterol content and a strong decrease in ethanol, heat shock and high osmolarity resistance. Surprisingly, the quadruple deletant and LAM2/LAM4 double deletion strain showed increased tolerance to the azole antifungals clotrimazole and miconazole. This effect was not associated with an increased rate of ABC-transporter substrate efflux. Possibly, increased sterol pool in the LAM deletion strains postpones the effect of azoles on cell growth. Alternatively, LAM deletions might alleviate the toxic effect of sterols as Lam proteins can transport toxic sterol biosynthesis intermediates into membrane compartments that are sensitive to these compounds. Our findings reveal novel biological roles of LAM genes in stress tolerance and suggest that mutations in these genes may confer upregulation of a mechanism that provides resistance to azole antifungals in pathogenic fungi.
format Online
Article
Text
id pubmed-6997477
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-69974772020-02-11 LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles Sokolov, Svyatoslav S. Vorobeva, Margarita A. Smirnova, Alexandra I. Smirnova, Ekaterina A. Trushina, Nataliya I. Galkina, Kseniia V. Severin, Fedor F. Knorre, Dmitry A. Front Microbiol Microbiology Lam proteins transport sterols between the membranes of different cellular compartments. In Saccharomyces cerevisiae, the LAM gene family consists of three pairs of paralogs. Because the function of paralogous genes can be redundant, the phenotypes of only a small number of LAM gene deletions have been reported; thus, the role of these genes in yeast physiology is still unclear. Here, we surveyed the phenotypes of double and quadruple deletants of paralogous LAM2(YSP2)/LAM4 and LAM1(YSP1)/LAM3(SIP3) genes that encode proteins localized in the junctions of the plasma membrane and endoplasmic reticulum. The quadruple deletant showed increased sterol content and a strong decrease in ethanol, heat shock and high osmolarity resistance. Surprisingly, the quadruple deletant and LAM2/LAM4 double deletion strain showed increased tolerance to the azole antifungals clotrimazole and miconazole. This effect was not associated with an increased rate of ABC-transporter substrate efflux. Possibly, increased sterol pool in the LAM deletion strains postpones the effect of azoles on cell growth. Alternatively, LAM deletions might alleviate the toxic effect of sterols as Lam proteins can transport toxic sterol biosynthesis intermediates into membrane compartments that are sensitive to these compounds. Our findings reveal novel biological roles of LAM genes in stress tolerance and suggest that mutations in these genes may confer upregulation of a mechanism that provides resistance to azole antifungals in pathogenic fungi. Frontiers Media S.A. 2020-01-28 /pmc/articles/PMC6997477/ /pubmed/32047490 http://dx.doi.org/10.3389/fmicb.2020.00038 Text en Copyright © 2020 Sokolov, Vorobeva, Smirnova, Smirnova, Trushina, Galkina, Severin and Knorre. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Sokolov, Svyatoslav S.
Vorobeva, Margarita A.
Smirnova, Alexandra I.
Smirnova, Ekaterina A.
Trushina, Nataliya I.
Galkina, Kseniia V.
Severin, Fedor F.
Knorre, Dmitry A.
LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles
title LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles
title_full LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles
title_fullStr LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles
title_full_unstemmed LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles
title_short LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles
title_sort lam genes contribute to environmental stress tolerance but sensibilize yeast cells to azoles
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997477/
https://www.ncbi.nlm.nih.gov/pubmed/32047490
http://dx.doi.org/10.3389/fmicb.2020.00038
work_keys_str_mv AT sokolovsvyatoslavs lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles
AT vorobevamargaritaa lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles
AT smirnovaalexandrai lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles
AT smirnovaekaterinaa lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles
AT trushinanataliyai lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles
AT galkinakseniiav lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles
AT severinfedorf lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles
AT knorredmitrya lamgenescontributetoenvironmentalstresstolerancebutsensibilizeyeastcellstoazoles