The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains

ABSTRACT Sensing external signals and transducing these into intracellular responses requires a molecular signaling system that is crucial for every living organism. Two important eukaryotic signal transduction pathways that are often interlinked are G-protein signaling and phospholipid signaling. H...

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Autores principales:	D. Johan van den Hoogen, Harold J. G. Meijer, Michael F. Seidl, Francine Govers
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	G-protein-coupled receptors Phytophthora cell signaling oomycetes phospholipid-mediated signaling Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/72acb50792694eddac0ee0540081ca4d
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spelling	oai:doaj.org-article:72acb50792694eddac0ee0540081ca4d2021-11-15T15:53:25ZThe Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains10.1128/mBio.02119-172150-7511https://doaj.org/article/72acb50792694eddac0ee0540081ca4d2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02119-17https://doaj.org/toc/2150-7511ABSTRACT Sensing external signals and transducing these into intracellular responses requires a molecular signaling system that is crucial for every living organism. Two important eukaryotic signal transduction pathways that are often interlinked are G-protein signaling and phospholipid signaling. Heterotrimeric G-protein subunits activated by G-protein-coupled receptors (GPCRs) are typical stimulators of phospholipid signaling enzymes such as phosphatidylinositol phosphate kinases (PIPKs) or phospholipase C (PLC). However, a direct connection between the two pathways likely exists in oomycetes and slime molds, as they possess a unique class of GPCRs that have a PIPK as an accessory domain. In principle, these so-called GPCR-PIPKs have the capacity of perceiving an external signal (via the GPCR domain) that, via PIPK, directly activates downstream phospholipid signaling. Here we reveal the sporadic occurrence of GPCR-PIPKs in all eukaryotic supergroups, except for plants. Notably, all species having GPCR-PIPKs are unicellular microorganisms that favor aquatic environments. Phylogenetic analysis revealed that GPCR-PIPKs are likely ancestral to eukaryotes and significantly expanded in the last common ancestor of oomycetes. In addition to GPCR-PIPKs, we identified five hitherto-unknown classes of GPCRs with accessory domains, four of which are universal players in signal transduction. Similarly to GPCR-PIPKs, this enables a direct coupling between extracellular sensing and downstream signaling. Overall, our findings point to an ancestral signaling system in eukaryotes where GPCR-mediated sensing is directly linked to downstream responses. IMPORTANCE G-protein-coupled receptors (GPCRs) are central sensors that activate eukaryotic signaling and are the primary targets of human drugs. In this report, we provide evidence for the widespread though limited presence of a novel class of GPCRs in a variety of unicellular eukaryotes. These include free-living organisms and organisms that are pathogenic for plants, animals, and humans. The novel GPCRs have a C-terminal phospholipid kinase domain, pointing to a direct link between sensing external signals via GPCRs and downstream intracellular phospholipid signaling. Genes encoding these receptors were likely present in the last common eukaryotic ancestor and were lost during the evolution of higher eukaryotes. We further describe five other types of GPCRs with a catalytic accessory domain, the so-called GPCR-bigrams, four of which may potentially have a role in signaling. These findings shed new light onto signal transduction in microorganisms and provide evidence for alternative eukaryotic signaling pathways.D. Johan van den HoogenHarold J. G. MeijerMichael F. SeidlFrancine GoversAmerican Society for MicrobiologyarticleG-protein-coupled receptorsPhytophthoracell signalingoomycetesphospholipid-mediated signalingMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	G-protein-coupled receptors Phytophthora cell signaling oomycetes phospholipid-mediated signaling Microbiology QR1-502
spellingShingle	G-protein-coupled receptors Phytophthora cell signaling oomycetes phospholipid-mediated signaling Microbiology QR1-502 D. Johan van den Hoogen Harold J. G. Meijer Michael F. Seidl Francine Govers The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains
description	ABSTRACT Sensing external signals and transducing these into intracellular responses requires a molecular signaling system that is crucial for every living organism. Two important eukaryotic signal transduction pathways that are often interlinked are G-protein signaling and phospholipid signaling. Heterotrimeric G-protein subunits activated by G-protein-coupled receptors (GPCRs) are typical stimulators of phospholipid signaling enzymes such as phosphatidylinositol phosphate kinases (PIPKs) or phospholipase C (PLC). However, a direct connection between the two pathways likely exists in oomycetes and slime molds, as they possess a unique class of GPCRs that have a PIPK as an accessory domain. In principle, these so-called GPCR-PIPKs have the capacity of perceiving an external signal (via the GPCR domain) that, via PIPK, directly activates downstream phospholipid signaling. Here we reveal the sporadic occurrence of GPCR-PIPKs in all eukaryotic supergroups, except for plants. Notably, all species having GPCR-PIPKs are unicellular microorganisms that favor aquatic environments. Phylogenetic analysis revealed that GPCR-PIPKs are likely ancestral to eukaryotes and significantly expanded in the last common ancestor of oomycetes. In addition to GPCR-PIPKs, we identified five hitherto-unknown classes of GPCRs with accessory domains, four of which are universal players in signal transduction. Similarly to GPCR-PIPKs, this enables a direct coupling between extracellular sensing and downstream signaling. Overall, our findings point to an ancestral signaling system in eukaryotes where GPCR-mediated sensing is directly linked to downstream responses. IMPORTANCE G-protein-coupled receptors (GPCRs) are central sensors that activate eukaryotic signaling and are the primary targets of human drugs. In this report, we provide evidence for the widespread though limited presence of a novel class of GPCRs in a variety of unicellular eukaryotes. These include free-living organisms and organisms that are pathogenic for plants, animals, and humans. The novel GPCRs have a C-terminal phospholipid kinase domain, pointing to a direct link between sensing external signals via GPCRs and downstream intracellular phospholipid signaling. Genes encoding these receptors were likely present in the last common eukaryotic ancestor and were lost during the evolution of higher eukaryotes. We further describe five other types of GPCRs with a catalytic accessory domain, the so-called GPCR-bigrams, four of which may potentially have a role in signaling. These findings shed new light onto signal transduction in microorganisms and provide evidence for alternative eukaryotic signaling pathways.
format	article
author	D. Johan van den Hoogen Harold J. G. Meijer Michael F. Seidl Francine Govers
author_facet	D. Johan van den Hoogen Harold J. G. Meijer Michael F. Seidl Francine Govers
author_sort	D. Johan van den Hoogen
title	The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains
title_short	The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains
title_full	The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains
title_fullStr	The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains
title_full_unstemmed	The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains
title_sort	ancient link between g-protein-coupled receptors and c-terminal phospholipid kinase domains
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/72acb50792694eddac0ee0540081ca4d
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The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid Kinase Domains

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