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Neuron. 2019 Apr 3;102(1):184-201.e8. doi: 10.1016/j.neuron.2019.01.030. Epub 2019 Feb 13.

Feedback-Driven Mechanisms between Microtubules and the Endoplasmic Reticulum Instruct Neuronal Polarity.

Author information

1
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, the Netherlands. Electronic address: g.c.fariasgaldames@uu.nl.
2
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, the Netherlands.
3
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, the Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, the Netherlands.
4
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, the Netherlands.
5
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, the Netherlands. Electronic address: c.hoogenraad@uu.nl.

Abstract

Establishment of neuronal polarity depends on local microtubule (MT) reorganization. The endoplasmic reticulum (ER) consists of cisternae and tubules and, like MTs, forms an extensive network throughout the entire cell. How the two networks interact and control neuronal development is an outstanding question. Here we show that the interplay between MTs and the ER is essential for neuronal polarity. ER tubules localize within the axon, whereas ER cisternae are retained in the somatodendritic domain. MTs are essential for axonal ER tubule stabilization, and, reciprocally, the ER is required for stabilizing and organizing axonal MTs. Recruitment of ER tubules into one minor neurite initiates axon formation, whereas ER retention in the perinuclear area or disruption of ER tubules prevent neuronal polarization. The ER-shaping protein P180, present in axonal ER tubules, controls axon specification by regulating local MT remodeling. We propose a model in which feedback-driven regulation between the ER and MTs instructs neuronal polarity.

KEYWORDS:

ER cisternae; ER tubules; ER-shaping proteins; MT-driven motors; axon specification; endoplasmic reticulum; microtubule dynamics; microtubules; neuronal polarity; neurons

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