Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

p75NTR and DR6 regulate distinct phases of axon degeneration demarcated by spheroid rupture

Yu Yong, Kanchana Gamage, Irene Cheng, Kelly Barford, Anthony Spano, Bettina Winckler, Christopher Deppmann
doi: https://doi.org/10.1101/710111
Yu Yong
Department of Biology, University of Virginia, Charlottesville, VA, 22903, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kanchana Gamage
Department of Cell Biology, University of Virginia, Charlottesville, VA, 22903, USAAmgen, Massachusetts & Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irene Cheng
Department of Biology, University of Virginia, Charlottesville, VA, 22903, USANeuroscience Graduate Program, University of Virginia, Charlottesville, VA, 22903, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kelly Barford
Neuroscience Graduate Program, University of Virginia, Charlottesville, VA, 22903, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony Spano
Department of Biology, University of Virginia, Charlottesville, VA, 22903, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bettina Winckler
Department of Cell Biology, University of Virginia, Charlottesville, VA, 22903, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher Deppmann
Department of Biology, University of Virginia, Charlottesville, VA, 22903, USANeuroscience Graduate Program, University of Virginia, Charlottesville, VA, 22903, USADepartment of Cell Biology, University of Virginia, Charlottesville, VA, 22903, USADepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22903, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: deppmann@virginia.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The regressive events associated with trophic deprivation are critical for sculpting a functional nervous system. After nerve growth factor withdrawal, sympathetic axons maintain their structural integrity for roughly 18 hours (latent phase) followed by a rapid and near unison disassembly of axons over the next 3 hours (catastrophic phase). Here we examine the molecular basis by which axons transition from latent to catastrophic phases of degeneration following trophic withdrawal. Prior to catastrophic degeneration, we observed an increase in intra-axonal calcium. This calcium flux is accompanied by p75 neurotrophic factor receptor (NTR)-Rho-actin dependent expansion of calcium rich axonal spheroids that eventually rupture, releasing their contents to the extracellular space. Conditioned media derived from degenerating axons is capable of hastening transition into the catastrophic phase of degeneration. We also found that death receptor 6 (DR6) but not p75NTR is required for transition into the catastrophic phase in response to conditioned media but not for the intra-axonal calcium flux, spheroid formation, or rupture that occurs toward the end of latency. Our results support the existence of an inter-axonal degenerative signal that promotes catastrophic degeneration among trophically deprived axons.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted July 20, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
p75NTR and DR6 regulate distinct phases of axon degeneration demarcated by spheroid rupture
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
p75NTR and DR6 regulate distinct phases of axon degeneration demarcated by spheroid rupture
Yu Yong, Kanchana Gamage, Irene Cheng, Kelly Barford, Anthony Spano, Bettina Winckler, Christopher Deppmann
bioRxiv 710111; doi: https://doi.org/10.1101/710111
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
p75NTR and DR6 regulate distinct phases of axon degeneration demarcated by spheroid rupture
Yu Yong, Kanchana Gamage, Irene Cheng, Kelly Barford, Anthony Spano, Bettina Winckler, Christopher Deppmann
bioRxiv 710111; doi: https://doi.org/10.1101/710111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (1530)
  • Biochemistry (2488)
  • Bioengineering (1745)
  • Bioinformatics (9696)
  • Biophysics (3912)
  • Cancer Biology (2976)
  • Cell Biology (4210)
  • Clinical Trials (135)
  • Developmental Biology (2636)
  • Ecology (4107)
  • Epidemiology (2033)
  • Evolutionary Biology (6906)
  • Genetics (5217)
  • Genomics (6516)
  • Immunology (2191)
  • Microbiology (6967)
  • Molecular Biology (2763)
  • Neuroscience (17334)
  • Paleontology (126)
  • Pathology (430)
  • Pharmacology and Toxicology (708)
  • Physiology (1061)
  • Plant Biology (2496)
  • Scientific Communication and Education (646)
  • Synthetic Biology (832)
  • Systems Biology (2690)
  • Zoology (432)