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PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury

Glial cells are exquisitely sensitive to neuronal injury but mechanisms by which glia establish competence to respond to injury, continuously gauge neuronal health, and rapidly activate reactive responses remain poorly defined. Here, we show glial PI3K signaling in the uninjured brain regulates base...

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Autores principales: Doherty, Johnna, Sheehan, Amy E., Bradshaw, Rachel, Fox, A. Nicole, Lu, Tsai-Yi, Freeman, Marc R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219656/
https://www.ncbi.nlm.nih.gov/pubmed/25369313
http://dx.doi.org/10.1371/journal.pbio.1001985
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author Doherty, Johnna
Sheehan, Amy E.
Bradshaw, Rachel
Fox, A. Nicole
Lu, Tsai-Yi
Freeman, Marc R.
author_facet Doherty, Johnna
Sheehan, Amy E.
Bradshaw, Rachel
Fox, A. Nicole
Lu, Tsai-Yi
Freeman, Marc R.
author_sort Doherty, Johnna
collection PubMed
description Glial cells are exquisitely sensitive to neuronal injury but mechanisms by which glia establish competence to respond to injury, continuously gauge neuronal health, and rapidly activate reactive responses remain poorly defined. Here, we show glial PI3K signaling in the uninjured brain regulates baseline levels of Draper, a receptor essential for Drosophila glia to sense and respond to axonal injury. After injury, Draper levels are up-regulated through a Stat92E-modulated, injury-responsive enhancer element within the draper gene. Surprisingly, canonical JAK/STAT signaling does not regulate draper expression. Rather, we find injury-induced draper activation is downstream of the Draper/Src42a/Shark/Rac1 engulfment signaling pathway. Thus, PI3K signaling and Stat92E are critical in vivo regulators of glial responsiveness to axonal injury. We provide evidence for a positive auto-regulatory mechanism whereby signaling through the injury-responsive Draper receptor leads to Stat92E-dependent, transcriptional activation of the draper gene. We propose that Drosophila glia use this auto-regulatory loop as a mechanism to adjust their reactive state following injury.
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spelling pubmed-42196562014-11-12 PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury Doherty, Johnna Sheehan, Amy E. Bradshaw, Rachel Fox, A. Nicole Lu, Tsai-Yi Freeman, Marc R. PLoS Biol Research Article Glial cells are exquisitely sensitive to neuronal injury but mechanisms by which glia establish competence to respond to injury, continuously gauge neuronal health, and rapidly activate reactive responses remain poorly defined. Here, we show glial PI3K signaling in the uninjured brain regulates baseline levels of Draper, a receptor essential for Drosophila glia to sense and respond to axonal injury. After injury, Draper levels are up-regulated through a Stat92E-modulated, injury-responsive enhancer element within the draper gene. Surprisingly, canonical JAK/STAT signaling does not regulate draper expression. Rather, we find injury-induced draper activation is downstream of the Draper/Src42a/Shark/Rac1 engulfment signaling pathway. Thus, PI3K signaling and Stat92E are critical in vivo regulators of glial responsiveness to axonal injury. We provide evidence for a positive auto-regulatory mechanism whereby signaling through the injury-responsive Draper receptor leads to Stat92E-dependent, transcriptional activation of the draper gene. We propose that Drosophila glia use this auto-regulatory loop as a mechanism to adjust their reactive state following injury. Public Library of Science 2014-11-04 /pmc/articles/PMC4219656/ /pubmed/25369313 http://dx.doi.org/10.1371/journal.pbio.1001985 Text en © 2014 Doherty et al 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
Doherty, Johnna
Sheehan, Amy E.
Bradshaw, Rachel
Fox, A. Nicole
Lu, Tsai-Yi
Freeman, Marc R.
PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury
title PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury
title_full PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury
title_fullStr PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury
title_full_unstemmed PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury
title_short PI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury
title_sort pi3k signaling and stat92e converge to modulate glial responsiveness to axonal injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219656/
https://www.ncbi.nlm.nih.gov/pubmed/25369313
http://dx.doi.org/10.1371/journal.pbio.1001985
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