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Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1823-8. doi: 10.1073/pnas.1514943113. Epub 2016 Feb 2.

Axons provide the secretory machinery for trafficking of voltage-gated sodium channels in peripheral nerve.

Author information

1
Program of Physiology and Biophysics, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile;
2
Instituto de Biología, Laboratorio de Microscopía Electrónica, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile;
3
Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
4
Program of Physiology and Biophysics, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile; andres@neuro.med.uchile.cl.

Abstract

The regulation of the axonal proteome is key to generate and maintain neural function. Fast and slow axoplasmic waves have been known for decades, but alternative mechanisms to control the abundance of axonal proteins based on local synthesis have also been identified. The presence of the endoplasmic reticulum has been documented in peripheral axons, but it is still unknown whether this localized organelle participates in the delivery of axonal membrane proteins. Voltage-gated sodium channels are responsible for action potentials and are mostly concentrated in the axon initial segment and nodes of Ranvier. Despite their fundamental role, little is known about the intracellular trafficking mechanisms that govern their availability in mature axons. Here we describe the secretory machinery in axons and its contribution to plasma membrane delivery of sodium channels. The distribution of axonal secretory components was evaluated in axons of the sciatic nerve and in spinal nerve axons after in vivo electroporation. Intracellular protein trafficking was pharmacologically blocked in vivo and in vitro. Axonal voltage-gated sodium channel mRNA and local trafficking were examined by RT-PCR and a retention-release methodology. We demonstrate that mature axons contain components of the endoplasmic reticulum and other biosynthetic organelles. Axonal organelles and sodium channel localization are sensitive to local blockade of the endoplasmic reticulum to Golgi transport. More importantly, secretory organelles are capable of delivering sodium channels to the plasma membrane in isolated axons, demonstrating an intrinsic capacity of the axonal biosynthetic route in regulating the axonal proteome in mammalian axons.

KEYWORDS:

axon; endoplasmic reticulum; trafficking

PMID:
26839409
PMCID:
PMC4763731
DOI:
10.1073/pnas.1514943113
[Indexed for MEDLINE]
Free PMC Article

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