An Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH

ABSTRACT In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a...

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Autores principales: Yu Tang, Yuantai Wu, Sarah E. Herlihy, Francisco J. Brito-Aleman, Jose H. Ting, Chris Janetopoulos, Richard H. Gomer
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:7addfcf8d05948fa8ec34887df7d8be02021-11-15T15:53:25ZAn Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH10.1128/mBio.02443-172150-7511https://doaj.org/article/7addfcf8d05948fa8ec34887df7d8be02018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02443-17https://doaj.org/toc/2150-7511ABSTRACT In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe Dictyostelium discoideum. AprA is a chemorepellent for and inhibits the proliferation of D. discoideum. We previously found that cells sense AprA using G proteins, suggesting the existence of a G protein-coupled AprA receptor. To identify the AprA receptor, we screened mutants lacking putative G protein-coupled receptors. We found that, compared to the wild-type strain, cells lacking putative receptor GrlH (grlH¯ cells) show rapid proliferation, do not have large numbers of cells moving away from the edges of colonies, are insensitive to AprA-induced proliferation inhibition and chemorepulsion, and have decreased AprA binding. Expression of GrlH in grlH¯ cells (grlH¯/grlHOE) rescues the phenotypes described above. These data indicate that AprA signaling may be mediated by GrlH in D. discoideum. IMPORTANCE Little is known about how eukaryotic cells can count themselves and thus regulate the size of a tissue or density of cells. In addition, little is known about how eukaryotic cells can sense a repellant signal and move away from the source of the repellant, for instance, to organize the movement of cells in a developing embryo or to move immune cells out of a tissue. In this study, we found that a eukaryotic microbe uses G protein-coupled receptors to mediate both cell density sensing and chemorepulsion.Yu TangYuantai WuSarah E. HerlihyFrancisco J. Brito-AlemanJose H. TingChris JanetopoulosRichard H. GomerAmerican Society for Microbiologyarticlecell density sensingchemorepulsionDictyosteliumG-protein-coupled receptorscell proliferationquorum sensingMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution DOAJ
collection DOAJ
language EN
topic cell density sensing
chemorepulsion
Dictyostelium
G-protein-coupled receptors
cell proliferation
quorum sensing
Microbiology
QR1-502
spellingShingle cell density sensing
chemorepulsion
Dictyostelium
G-protein-coupled receptors
cell proliferation
quorum sensing
Microbiology
QR1-502
Yu Tang
Yuantai Wu
Sarah E. Herlihy
Francisco J. Brito-Aleman
Jose H. Ting
Chris Janetopoulos
Richard H. Gomer
An Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
description ABSTRACT In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe Dictyostelium discoideum. AprA is a chemorepellent for and inhibits the proliferation of D. discoideum. We previously found that cells sense AprA using G proteins, suggesting the existence of a G protein-coupled AprA receptor. To identify the AprA receptor, we screened mutants lacking putative G protein-coupled receptors. We found that, compared to the wild-type strain, cells lacking putative receptor GrlH (grlH¯ cells) show rapid proliferation, do not have large numbers of cells moving away from the edges of colonies, are insensitive to AprA-induced proliferation inhibition and chemorepulsion, and have decreased AprA binding. Expression of GrlH in grlH¯ cells (grlH¯/grlHOE) rescues the phenotypes described above. These data indicate that AprA signaling may be mediated by GrlH in D. discoideum. IMPORTANCE Little is known about how eukaryotic cells can count themselves and thus regulate the size of a tissue or density of cells. In addition, little is known about how eukaryotic cells can sense a repellant signal and move away from the source of the repellant, for instance, to organize the movement of cells in a developing embryo or to move immune cells out of a tissue. In this study, we found that a eukaryotic microbe uses G protein-coupled receptors to mediate both cell density sensing and chemorepulsion.
format article
author Yu Tang
Yuantai Wu
Sarah E. Herlihy
Francisco J. Brito-Aleman
Jose H. Ting
Chris Janetopoulos
Richard H. Gomer
author_facet Yu Tang
Yuantai Wu
Sarah E. Herlihy
Francisco J. Brito-Aleman
Jose H. Ting
Chris Janetopoulos
Richard H. Gomer
author_sort Yu Tang
title An Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
title_short An Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
title_full An Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
title_fullStr An Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
title_full_unstemmed An Autocrine Proliferation Repressor Regulates <italic toggle="yes">Dictyostelium discoideum</italic> Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
title_sort autocrine proliferation repressor regulates <italic toggle="yes">dictyostelium discoideum</italic> proliferation and chemorepulsion using the g protein-coupled receptor grlh
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/7addfcf8d05948fa8ec34887df7d8be0
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