Unconventional secretory processing diversifies neuronal ion channel properties

Elife. 2016 Sep 28;5:e20609. doi: 10.7554/eLife.20609.

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.

Keywords: cell biology; glycosylation; golgi-bypass; neuronal membrane proteins; neuroscience; rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Chemistry
  • Cell Line
  • Glycosylation*
  • Immunoblotting
  • Ion Channels / metabolism*
  • Mammals
  • Mass Spectrometry
  • Membrane Proteins / metabolism
  • Neurons / chemistry*
  • Optical Imaging

Substances

  • Ion Channels
  • Membrane Proteins

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.