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Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration.

Accepted version
Peer-reviewed

Type

Article

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Authors

Öztürk, Zeynep 
O'Kane, Cahir J 
Pérez-Moreno, Juan José 

Abstract

The physical continuity of axons over long cellular distances poses challenges for their maintenance. One organelle that faces this challenge is endoplasmic reticulum (ER); unlike other intracellular organelles, this forms a physically continuous network throughout the cell, with a single membrane and a single lumen. In axons, ER is mainly smooth, forming a tubular network with occasional sheets or cisternae and low amounts of rough ER. It has many potential roles: lipid biosynthesis, glucose homeostasis, a Ca2+ store, protein export, and contacting and regulating other organelles. This tubular network structure is determined by ER-shaping proteins, mutations in some of which are causative for neurodegenerative disorders such as hereditary spastic paraplegia (HSP). While axonal ER shares many features with the tubular ER network in other contexts, these features must be adapted to the long and narrow dimensions of axons. ER appears to be physically continuous throughout axons, over distances that are enormous on a subcellular scale. It is therefore a potential channel for long-distance or regional communication within neurons, independent of action potentials or physical transport of cargos, but involving its physiological roles such as Ca2+ or organelle homeostasis. Despite its apparent stability, axonal ER is highly dynamic, showing features like anterograde and retrograde transport, potentially reflecting continuous fusion and breakage of the network. Here we discuss the transport processes that must contribute to this dynamic behavior of ER. We also discuss the model that these processes underpin a homeostatic process that ensures both enough ER to maintain continuity of the network and repair breaks in it, but not too much ER that might disrupt local cellular physiology. Finally, we discuss how failure of ER organization in axons could lead to axon degenerative diseases, and how a requirement for ER continuity could make distal axons most susceptible to degeneration in conditions that disrupt ER continuity.

Description

Keywords

axonal transport, calcium stores, endoplasmic reticulum, hereditary spastic paraplegia, neurodegeneration, organelle contact sites, smooth ER

Journal Title

Front Neurosci

Conference Name

Journal ISSN

1662-4548
1662-453X

Volume Title

14

Publisher

Frontiers Media SA

Rights

All rights reserved
Sponsorship
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (745007)
Biotechnology and Biological Sciences Research Council (BB/S001212/1)
Medical Research Council (MR/S011226/1)
ZÖ is funded by The Republic of Turkey Ministry of National Education scholarship (MEB1416) from Turkish Embassy. JJPM is supported by Marie Sklodowska-Curie fellowship 745007 from the European Union Horizon 2020 research and innovation program. The work of CJO’K is funded by grant BB/S001212/1 from the UK Biotechnology and Biological Sciences Research Council, and grant MR/S011226/1 from the UK Medical Research Council.