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Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

Published version
Peer-reviewed

Type

Article

Change log

Authors

Yalçın, B 
Stofanko, M 
O'Sullivan, NC 
Kang, ZH 

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.

Description

Keywords

D. melanogaster, axon, axon degeneration, cell biology, endoplasmic reticulum, hereditary spastic paraplegia, neuroscience, smooth endoplasmic reticulum, ultrastructure, Animals, Axonal Transport, Axons, Disease Models, Animal, Drosophila Proteins, Drosophila melanogaster, Endoplasmic Reticulum, Gene Expression, Humans, Larva, Membrane Transport Proteins, Mutation, Phylogeny, Protein Isoforms, Spastic Paraplegia, Hereditary

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

6

Publisher

eLife Sciences Publications Ltd
Sponsorship
Wellcome Trust (081386/Z/06/Z)
Motor Neurone Disease Association (None)
European Commission (220851)
European Commission (220874)
European Commission (236777)
Biotechnology and Biological Sciences Research Council (BB/L021706/1)
European Commission (660516)
RCUK | Biotechnology and Biological Sciences Research Council (BBSRC): Lu Zhao, Cahir J O'Kane, BB/L021706/1; Wellcome: Martin Stofanko, Cahir J O'Kane, 08136; European Commission (EC): Lu Zhao, Niamh C O'Sullivan, Sophie Zaessinger, Olivier Blard, MCSA fellowships 220851,220874,236777,660516; Yousef Jameel Foundation: Belgin Yalçın; Singapore A*STAR Scholarship: Zi Han Kang, BM/RES/07/005; Cambridge Commonwealth, European and International Trust (Cambridge Commonwealth, European & International Trust): Belgin Yalçın, Anood Sohail; Pakistan Higher Education Council Scholarship: Anood Sohail; Motor Neurone Disease Association (MNDA): Alex L Patto, Studentship 861-792 The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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