A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast

Abstract MAPK pathways regulate different responses yet can share common components. Although core regulators of MAPK pathways are well known, new pathway regulators continue to be identified. Overexpression screens can uncover new roles for genes in biological processes and are well suited to ident...

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Autores principales:	Sheida Jamalzadeh, Atindra N. Pujari, Paul J. Cullen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2b17757a5304cadb88584e2e078631d
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spelling	oai:doaj.org-article:b2b17757a5304cadb88584e2e078631d2021-12-02T12:42:27ZA Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast10.1038/s41598-020-78470-42045-2322https://doaj.org/article/b2b17757a5304cadb88584e2e078631d2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78470-4https://doaj.org/toc/2045-2322Abstract MAPK pathways regulate different responses yet can share common components. Although core regulators of MAPK pathways are well known, new pathway regulators continue to be identified. Overexpression screens can uncover new roles for genes in biological processes and are well suited to identify essential genes that cannot be evaluated by gene deletion analysis. In this study, a genome-wide screen was performed to identify genes that, when overexpressed, induce a reporter (FUS1-HIS3) that responds to ERK-type pathways (Mating and filamentous growth or fMAPK) but not p38-type pathways (HOG) in yeast. Approximately 4500 plasmids overexpressing individual yeast genes were introduced into strains containing the reporter by high-throughput transformation. Candidate genes were identified by measuring growth as a readout of reporter activity. Fourteen genes were identified and validated by re-testing: two were metabolic controls (HIS3, ATR1), five had established roles in regulating ERK-type pathways (STE4, STE7, BMH1, BMH2, MIG2) and seven represent potentially new regulators of MAPK signaling (RRN6, CIN5, MRS6, KAR2, TFA1, RSC3, RGT2). MRS6 encodes a Rab escort protein and effector of the TOR pathway that plays a role in nutrient signaling. MRS6 overexpression stimulated invasive growth and phosphorylation of the ERK-type fMAPK, Kss1. Overexpression of MRS6 reduced the osmotolerance of cells and phosphorylation of the p38/HOG MAPK, Hog1. Mrs6 interacted with the PAK kinase Ste20 and MAPKK Ste7 by two-hybrid analysis. Based on these results, Mrs6 may selectively propagate an ERK-dependent signal. Identifying new regulators of MAPK pathways may provide new insights into signal integration among core cellular processes and the execution of pathway-specific responses.Sheida JamalzadehAtindra N. PujariPaul J. CullenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-19 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sheida Jamalzadeh Atindra N. Pujari Paul J. Cullen A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast
description	Abstract MAPK pathways regulate different responses yet can share common components. Although core regulators of MAPK pathways are well known, new pathway regulators continue to be identified. Overexpression screens can uncover new roles for genes in biological processes and are well suited to identify essential genes that cannot be evaluated by gene deletion analysis. In this study, a genome-wide screen was performed to identify genes that, when overexpressed, induce a reporter (FUS1-HIS3) that responds to ERK-type pathways (Mating and filamentous growth or fMAPK) but not p38-type pathways (HOG) in yeast. Approximately 4500 plasmids overexpressing individual yeast genes were introduced into strains containing the reporter by high-throughput transformation. Candidate genes were identified by measuring growth as a readout of reporter activity. Fourteen genes were identified and validated by re-testing: two were metabolic controls (HIS3, ATR1), five had established roles in regulating ERK-type pathways (STE4, STE7, BMH1, BMH2, MIG2) and seven represent potentially new regulators of MAPK signaling (RRN6, CIN5, MRS6, KAR2, TFA1, RSC3, RGT2). MRS6 encodes a Rab escort protein and effector of the TOR pathway that plays a role in nutrient signaling. MRS6 overexpression stimulated invasive growth and phosphorylation of the ERK-type fMAPK, Kss1. Overexpression of MRS6 reduced the osmotolerance of cells and phosphorylation of the p38/HOG MAPK, Hog1. Mrs6 interacted with the PAK kinase Ste20 and MAPKK Ste7 by two-hybrid analysis. Based on these results, Mrs6 may selectively propagate an ERK-dependent signal. Identifying new regulators of MAPK pathways may provide new insights into signal integration among core cellular processes and the execution of pathway-specific responses.
format	article
author	Sheida Jamalzadeh Atindra N. Pujari Paul J. Cullen
author_facet	Sheida Jamalzadeh Atindra N. Pujari Paul J. Cullen
author_sort	Sheida Jamalzadeh
title	A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast
title_short	A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast
title_full	A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast
title_fullStr	A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast
title_full_unstemmed	A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast
title_sort	rab escort protein regulates the mapk pathway that controls filamentous growth in yeast
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/b2b17757a5304cadb88584e2e078631d
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A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast

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