Dystroglycan is a scaffold for extracellular axon guidance decisions
- Oregon Health and Science University, United States
- Universite' Catholique de Louvain, Belgium
- Janelia Research Campus, Howard Hughes Medical Institute, United States
Abstract
Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories of extending axons throughout the mammalian brain and spinal cord. Dystroglycan operates primarily as an extracellular scaffold during axon guidance, as it functions non-cell autonomously and does not require signaling through its intracellular domain. We identify the transmembrane receptor Celsr3/Adgrc3 as a binding partner for Dystroglycan, and show that this interaction is critical for specific axon guidance events in vivo. These findings establish Dystroglycan as a multifunctional scaffold that coordinates extracellular matrix proteins, secreted cues, and transmembrane receptors to regulate axon guidance.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files
Article and author information
Author details
Funding
National Institutes of Health (NS091027)
- Kevin M Wright
Medical Research Foundation (N/A)
- Kevin M Wright
ARC (17/22-079)
- Fadel Tissir
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Carol A Mason, Columbia University, United States
Ethics
Animal experimentation: Mice were handled and bred in accordance with the Oregon Health and Science University IACUC guidelines, protocol #IP00000539.
Version history
- Received: September 18, 2018
- Accepted: February 13, 2019
- Accepted Manuscript published: February 13, 2019 (version 1)
- Version of Record published: February 28, 2019 (version 2)
Copyright
© 2019, Lindenmaier et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dystroglycan is a scaffold for extracellular axon guidance decisions
eLife 8:e42143.
https://doi.org/10.7554/eLife.42143
