Unconventional secretory processing diversifies neuronal ion channel properties.
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.
Max Planck Institute for Brain Research, Frankfurt, Germany.
Cyril
C
Hanus
Max Planck Institute for Brain Research, Frankfurt, Germany.
Helene
H
Geptin
Max Planck Institute for Brain Research, Frankfurt, Germany.
Georgi
G
Tushev
Max Planck Institute for Brain Research, Frankfurt, Germany.
Sakshi
S
Garg
Max Planck Institute for Brain Research, Frankfurt, Germany.
Beatriz
B
Alvarez-Castelao
Max Planck Institute for Brain Research, Frankfurt, Germany.
Sivakumar
S
Sambandan
Max Planck Institute for Brain Research, Frankfurt, Germany.
Lisa
L
Kochen
Max Planck Institute for Brain Research, Frankfurt, Germany.
Anne-Sophie
AS
Hafner
Max Planck Institute for Brain Research, Frankfurt, Germany.|Max Planck Institute for Biophysics, Frankfurt, Germany.
Julian D
JD
Langer
Max Planck Institute for Brain Research, Frankfurt, Germany.
Erin M
0000-0002-7053-1005
EM
Schuman
D000818:Animals; D001923:Brain Chemistry; D002460:Cell Line; D006031:Glycosylation; D015151:Immunoblotting; D007473:Ion Channels / Q000378:metabolism*; D008322:Mammals; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000737:chemistry*; D061848:Optical Imaging
D007473:Ion Channels; D008565:Membrane Proteins
cell biology; glycosylation; golgi-bypass; neuronal membrane proteins; neuroscience; rat
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