Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins
- University of Cambridge, United Kingdom
- University of Connecticut Health Center, United States
Abstract
Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.
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Author details
Funding
Biotechnology and Biological Sciences Research Council (BB/L021706/1)
- Lu Zhao
- Cahir J O'Kane
Wellcome (8136)
- Martin Stofanko
- Cahir J O'Kane
European Commission (MCSA fellowships 220851,220874,236777,660516)
- Lu Zhao
- Niamh C O'Sullivan
- Sophie Zaessinger
- Olivier Blard
Yousef Jameel Foundation
- Belgin Yalçın
Singapore A*STAR Scholarship (BM/RES/07/005)
- Zi Han Kang
Cambridge Commonwealth, European and International Trust
- Belgin Yalçın
- Anood Sohail
Pakistan Higher Education Council Scholarship
- Anood Sohail
Motor Neurone Disease Association (Studentship 861-792)
- Alex L Patto
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Yalçın 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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Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins
eLife 6:e23882.
https://doi.org/10.7554/eLife.23882
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