CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>

ABSTRACT Myxococcus xanthus serves as a model organism for development and complex signal transduction. Regulation of developmental aggregation and sporulation is controlled, in part, by the Che3 chemosensory system. The Che3 pathway consists of homologs to two methyl-accepting chemotaxis proteins (...

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Autores principales:	Jonathan W. Willett, John R. Kirby
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/451843aeac4246499f00d865eaa8e4cc
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spelling	oai:doaj.org-article:451843aeac4246499f00d865eaa8e4cc2021-11-15T15:38:45ZCrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>10.1128/mBio.00110-112150-7511https://doaj.org/article/451843aeac4246499f00d865eaa8e4cc2011-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00110-11https://doaj.org/toc/2150-7511ABSTRACT Myxococcus xanthus serves as a model organism for development and complex signal transduction. Regulation of developmental aggregation and sporulation is controlled, in part, by the Che3 chemosensory system. The Che3 pathway consists of homologs to two methyl-accepting chemotaxis proteins (MCPs), CheA, CheW, CheB, and CheR but not CheY. Instead, the output for Che3 is the NtrC homolog CrdA, which functions to regulate developmental gene expression. In this paper we have identified an additional kinase, CrdS, which directly regulates the phosphorylation state of CrdA. Both epistasis and in vitro phosphotransfer assays indicate that CrdS functions as part of the Che3 pathway and, in addition to CheA3, serves to regulate CrdA phosphorylation in M. xanthus. We provide kinetic data for CrdS autophosphorylation and demonstrate specificity for phosphotransfer from CrdS to CrdA. We further demonstrate that CheA3 destabilizes phosphorylated CrdA (CrdA~P), indicating that CheA3 likely acts as a phosphatase. Both CrdS and CheA3 control developmental progression by regulating the phosphorylation state of CrdA~P in the cell. These results support a model in which a classical two-component system and a chemosensory system act synergistically to control the activity of the response regulator CrdA. IMPORTANCE While phosphorylation-mediated signal transduction is well understood in prototypical chemotaxis and two-component systems (TCS), chemosensory regulation of alternative cellular functions (ACF) has not been clearly defined. The Che3 system in Myxococcus xanthus is a member of the ACF class of chemosensory systems and regulates development via the transcription factor CrdA (chemosensory regulator of development) (K. Wuichet and I. B. Zhulin, Sci. Signal. 3:ra50, 2010; J. R. Kirby and D. R. Zusman, Proc. Natl. Acad. Sci. U. S. A. 100:2008–2013, 2003). We have identified and characterized a homolog of NtrB, designated CrdS, capable of specifically phosphorylating the NtrC homolog CrdA in M. xanthus. Additionally, we demonstrate that the CrdSA two-component system is negatively regulated by CheA3, the central processor within the Che3 system of M. xanthus. To our knowledge, this study provides the first example of an ACF chemosensory system regulating a prototypical two-component system and extends our understanding of complex regulation of developmental signaling pathways.Jonathan W. WillettJohn R. KirbyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 4 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jonathan W. Willett John R. Kirby CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>
description	ABSTRACT Myxococcus xanthus serves as a model organism for development and complex signal transduction. Regulation of developmental aggregation and sporulation is controlled, in part, by the Che3 chemosensory system. The Che3 pathway consists of homologs to two methyl-accepting chemotaxis proteins (MCPs), CheA, CheW, CheB, and CheR but not CheY. Instead, the output for Che3 is the NtrC homolog CrdA, which functions to regulate developmental gene expression. In this paper we have identified an additional kinase, CrdS, which directly regulates the phosphorylation state of CrdA. Both epistasis and in vitro phosphotransfer assays indicate that CrdS functions as part of the Che3 pathway and, in addition to CheA3, serves to regulate CrdA phosphorylation in M. xanthus. We provide kinetic data for CrdS autophosphorylation and demonstrate specificity for phosphotransfer from CrdS to CrdA. We further demonstrate that CheA3 destabilizes phosphorylated CrdA (CrdA~P), indicating that CheA3 likely acts as a phosphatase. Both CrdS and CheA3 control developmental progression by regulating the phosphorylation state of CrdA~P in the cell. These results support a model in which a classical two-component system and a chemosensory system act synergistically to control the activity of the response regulator CrdA. IMPORTANCE While phosphorylation-mediated signal transduction is well understood in prototypical chemotaxis and two-component systems (TCS), chemosensory regulation of alternative cellular functions (ACF) has not been clearly defined. The Che3 system in Myxococcus xanthus is a member of the ACF class of chemosensory systems and regulates development via the transcription factor CrdA (chemosensory regulator of development) (K. Wuichet and I. B. Zhulin, Sci. Signal. 3:ra50, 2010; J. R. Kirby and D. R. Zusman, Proc. Natl. Acad. Sci. U. S. A. 100:2008–2013, 2003). We have identified and characterized a homolog of NtrB, designated CrdS, capable of specifically phosphorylating the NtrC homolog CrdA in M. xanthus. Additionally, we demonstrate that the CrdSA two-component system is negatively regulated by CheA3, the central processor within the Che3 system of M. xanthus. To our knowledge, this study provides the first example of an ACF chemosensory system regulating a prototypical two-component system and extends our understanding of complex regulation of developmental signaling pathways.
format	article
author	Jonathan W. Willett John R. Kirby
author_facet	Jonathan W. Willett John R. Kirby
author_sort	Jonathan W. Willett
title	CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>
title_short	CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>
title_full	CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>
title_fullStr	CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>
title_full_unstemmed	CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>
title_sort	crds and crda comprise a two-component system that is cooperatively regulated by the che3 chemosensory system in <named-content content-type="genus-species">myxococcus xanthus</named-content>
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/451843aeac4246499f00d865eaa8e4cc
work_keys_str_mv	AT jonathanwwillett crdsandcrdacompriseatwocomponentsystemthatiscooperativelyregulatedbytheche3chemosensorysysteminnamedcontentcontenttypegenusspeciesmyxococcusxanthusnamedcontent AT johnrkirby crdsandcrdacompriseatwocomponentsystemthatiscooperativelyregulatedbytheche3chemosensorysysteminnamedcontentcontenttypegenusspeciesmyxococcusxanthusnamedcontent
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CrdS and CrdA Comprise a Two-Component System That Is Cooperatively Regulated by the Che3 Chemosensory System in <named-content content-type="genus-species">Myxococcus xanthus</named-content>

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