Maintaining long, energetically demanding axons throughout the life of an animal is a major challenge for the nervous system. Specialized glia ensheathe axons and support their function and integrity throughout life, but glial support mechanisms remain poorly defined. Here, we identified a collection of secreted and transmembrane molecules required in glia for long-term axon survival in vivo. We showed that the majority of components of the TGFβ superfamily are required in glia for sensory neuron maintenance but not glial ensheathment of axons. In the absence of glial TGFβ signaling, neurons undergo age-dependent degeneration that can be rescued either by genetic blockade of Wallerian degeneration or caspase-dependent death. Blockade of glial TGFβ signaling results in increased ATP in glia that can be mimicked by enhancing glial mitochondrial biogenesis or suppressing glial monocarboxylate transporter function. We propose that glial TGFβ signaling supports axon survival and suppresses neurodegeneration through promoting glial metabolic support of neurons.
Skip Nav Destination
Article navigation
2 January 2023
Article|
November 18 2022
Glial TGFβ activity promotes neuron survival in peripheral nerves
Alexandria P. Lassetter
,
Alexandria P. Lassetter
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Search for other works by this author on:
Megan M. Corty
,
Megan M. Corty
(Conceptualization, Investigation, Methodology, Writing - review & editing)
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Search for other works by this author on:
Romina Barria
,
Romina Barria
(Investigation, Methodology)
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Search for other works by this author on:
Amy E. Sheehan
,
Amy E. Sheehan
(Investigation)
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Search for other works by this author on:
Jo Q. Hill
,
Jo Q. Hill
(Investigation)
2
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR
Search for other works by this author on:
Sue A. Aicher
,
Sue A. Aicher
(Funding acquisition, Methodology, Supervision, Writing - review & editing)
2
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR
Search for other works by this author on:
A. Nicole Fox
,
A. Nicole Fox
(Investigation, Methodology, Resources, Writing - review & editing)
3
University of Massachusetts Medical School, Worcester, MA
Search for other works by this author on:
Marc R. Freeman
(Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing)
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Correspondence to Marc R. Freeman: freemmar@ohsu.edu
Search for other works by this author on:
Alexandria P. Lassetter
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Megan M. Corty
Conceptualization, Investigation, Methodology, Writing - review & editing
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Romina Barria
Investigation, Methodology
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Amy E. Sheehan
Investigation
1
Vollum Institute, Oregon Health & Science University, Portland, OR
Jo Q. Hill
Investigation
2
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR
Sue A. Aicher
Funding acquisition, Methodology, Supervision, Writing - review & editing
2
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR
A. Nicole Fox
Investigation, Methodology, Resources, Writing - review & editing
3
University of Massachusetts Medical School, Worcester, MA
Correspondence to Marc R. Freeman: freemmar@ohsu.edu
Disclosures: The authors declare no competing interests exist.
Received:
November 11 2021
Revision Received:
September 06 2022
Accepted:
October 26 2022
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
National Institute of Neurological Disorders and Stroke
- Award Id(s): P30 NS061800
Funder(s):
National Institutes of Health
- Award Id(s): NS053538,NS112215
© 2022 Lassetter et al.
2022
Lassetter et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2023) 222 (1): e202111053.
Article history
Received:
November 11 2021
Revision Received:
September 06 2022
Accepted:
October 26 2022
Citation
Alexandria P. Lassetter, Megan M. Corty, Romina Barria, Amy E. Sheehan, Jo Q. Hill, Sue A. Aicher, A. Nicole Fox, Marc R. Freeman; Glial TGFβ activity promotes neuron survival in peripheral nerves. J Cell Biol 2 January 2023; 222 (1): e202111053. doi: https://doi.org/10.1083/jcb.202111053
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your Institution
774
Views
Advertisement
Advertisement