Unconventional secretory processing diversifies neuronal ion channel properties
- Max Planck Institute for Brain Research, Germany
- Max Planck Institute for Brain Research and Max Planck Institute for Biophysics, Germany
Abstract
N-glycosylation - the sequential addition of complex sugars to adhesion proteins, neurotransmitter receptors, ion channels and secreted trophic factors as they progress through the endoplasmic reticulum and the Golgi apparatus - is one of the most frequent protein modifications. In mammals, most organ-specific N-glycosylation events occur in the brain. Yet, little is known about the nature, function and regulation of N-glycosylation in neurons. Using imaging, quantitative immunoblotting and mass spectrometry, we show that hundreds of neuronal surface membrane proteins are core-glycosylated, resulting in the neuronal membrane displaying surprisingly high levels of glycosylation profiles that are classically associated with immature intracellular proteins. We report that while N-glycosylation is generally required for dendritic development and glutamate receptor surface expression, core-glycosylated proteins are sufficient to sustain these processes, and are thus functional. This atypical glycosylation of surface neuronal proteins can be attributed to a bypass or a hypo-function of the Golgi apparatus. Core-glycosylation is regulated by synaptic activity, modulates synaptic signaling and accelerates the turnover of GluA2-containing glutamate receptors, revealing a novel mechanism that controls the composition and sensing properties of the neuronal membrane.
Article and author information
Author details
Funding
European Research Council (DFG CRC 902)
- Erin M Schuman
European Research Council (1080)
- Erin M Schuman
DFG Cluster of Excellence for Macromolecular Complexes
- Erin M Schuman
Marie Curie, career integration grant
- Cyril Hanus
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- David D Ginty, Howard Hughes Medical Institute, Harvard Medical School, United States
Ethics
Animal experimentation: We hereby certify that all the experiments involving animals (i.e. postmortem tissue removal as defined in the {section sign} 4(3) of German animal welfare act) that were done in relation to our manuscript entitled "Unconventional secretory trafficking diversifies the properties of neuronal ion channels" were carried out in accordance with the European directive 2010/63/EU, the German animal welfare act, and the guidelines of the Federation ofLaboratory Animal Science Associations (FELASA) and the Max Planck Society.
Version history
- Received: August 14, 2016
- Accepted: September 22, 2016
- Accepted Manuscript published: September 28, 2016 (version 1)
- Accepted Manuscript updated: October 5, 2016 (version 2)
- Version of Record published: October 24, 2016 (version 3)
Copyright
© 2016, Hanus 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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Unconventional secretory processing diversifies neuronal ion channel properties
eLife 5:e20609.
https://doi.org/10.7554/eLife.20609
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