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The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum
In Dictyostelium discoideum, the secreted proteins AprA and CfaD function as reporters of cell density and regulate cell number by inhibiting proliferation at high cell densities. AprA also functions to disperse groups of cells at high density by acting as a chemorepellent. However, the signal trans...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010531/ https://www.ncbi.nlm.nih.gov/pubmed/24797076 http://dx.doi.org/10.1371/journal.pone.0096633 |
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author | Phillips, Jonathan E. Gomer, Richard H. |
author_facet | Phillips, Jonathan E. Gomer, Richard H. |
author_sort | Phillips, Jonathan E. |
collection | PubMed |
description | In Dictyostelium discoideum, the secreted proteins AprA and CfaD function as reporters of cell density and regulate cell number by inhibiting proliferation at high cell densities. AprA also functions to disperse groups of cells at high density by acting as a chemorepellent. However, the signal transduction pathways associated with AprA and CfaD are not clear, and little is known about how AprA affects the cytoskeleton to regulate cell movement. We found that the p21-activated kinase (PAK) family member PakD is required for both the proliferation-inhibiting activity of AprA and CfaD and the chemorepellent activity of AprA. Similar to cells lacking AprA or CfaD, cells lacking PakD proliferate to a higher cell density than wild-type cells. Recombinant AprA and CfaD inhibit the proliferation of wild-type cells but not cells lacking PakD. Like AprA and CfaD, PakD affects proliferation but does not significantly affect growth (the accumulation of mass) on a per-nucleus basis. In contrast to wild-type cells, cells lacking PakD are not repelled from a source of AprA, and colonies of cells lacking PakD expand at a slower rate than wild-type cells, indicating that PakD is required for AprA-mediated chemorepulsion. A PakD-GFP fusion protein localizes to an intracellular punctum that is not the nucleus or centrosome, and PakD-GFP is also occasionally observed at the rear cortex of moving cells. Vegetative cells lacking PakD show excessive actin-based filopodia-like structures, suggesting that PakD affects actin dynamics, consistent with previously characterized roles of PAK proteins in actin regulation. Together, our results implicate PakD in AprA/CfaD signaling and show that a PAK protein is required for proper chemorepulsive cell movement in Dictyostelium. |
format | Online Article Text |
id | pubmed-4010531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40105312014-05-09 The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum Phillips, Jonathan E. Gomer, Richard H. PLoS One Research Article In Dictyostelium discoideum, the secreted proteins AprA and CfaD function as reporters of cell density and regulate cell number by inhibiting proliferation at high cell densities. AprA also functions to disperse groups of cells at high density by acting as a chemorepellent. However, the signal transduction pathways associated with AprA and CfaD are not clear, and little is known about how AprA affects the cytoskeleton to regulate cell movement. We found that the p21-activated kinase (PAK) family member PakD is required for both the proliferation-inhibiting activity of AprA and CfaD and the chemorepellent activity of AprA. Similar to cells lacking AprA or CfaD, cells lacking PakD proliferate to a higher cell density than wild-type cells. Recombinant AprA and CfaD inhibit the proliferation of wild-type cells but not cells lacking PakD. Like AprA and CfaD, PakD affects proliferation but does not significantly affect growth (the accumulation of mass) on a per-nucleus basis. In contrast to wild-type cells, cells lacking PakD are not repelled from a source of AprA, and colonies of cells lacking PakD expand at a slower rate than wild-type cells, indicating that PakD is required for AprA-mediated chemorepulsion. A PakD-GFP fusion protein localizes to an intracellular punctum that is not the nucleus or centrosome, and PakD-GFP is also occasionally observed at the rear cortex of moving cells. Vegetative cells lacking PakD show excessive actin-based filopodia-like structures, suggesting that PakD affects actin dynamics, consistent with previously characterized roles of PAK proteins in actin regulation. Together, our results implicate PakD in AprA/CfaD signaling and show that a PAK protein is required for proper chemorepulsive cell movement in Dictyostelium. Public Library of Science 2014-05-05 /pmc/articles/PMC4010531/ /pubmed/24797076 http://dx.doi.org/10.1371/journal.pone.0096633 Text en © 2014 Phillips, Gomer http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Phillips, Jonathan E. Gomer, Richard H. The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum |
title | The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum
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title_full | The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum
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title_fullStr | The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum
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title_full_unstemmed | The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum
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title_short | The p21-Activated Kinase (PAK) Family Member PakD Is Required for Chemorepulsion and Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum
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title_sort | p21-activated kinase (pak) family member pakd is required for chemorepulsion and proliferation inhibition by autocrine signals in dictyostelium discoideum |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010531/ https://www.ncbi.nlm.nih.gov/pubmed/24797076 http://dx.doi.org/10.1371/journal.pone.0096633 |
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