Abstract
Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity and related diseases, but their mechanistic basis and significance are unclear. Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation. In exploring the basis of these N-glycosylation alterations, we discovered they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite. Golgi satellites that formed during neuronal excitation were in close association with ER exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130. They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway, or on surface glycoproteins taken up from the endocytic pathway. These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors. Neural activity thus boosts the activity of the dendrite’s satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites. This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction and disease.
| Original language | English (US) |
|---|---|
| Article number | e68910 |
| Journal | eLife |
| Volume | 10 |
| DOIs | |
| State | Published - Sep 2021 |
Funding
This work was financially supported by NIH RO1 DA035430, DA044760, and DA043361 (W. N. G.) R01 GM104010 (B.S.G.), T32 GM007183 (F.V.) and Peter F. McManus Foundation (W. N. G.). We thank Vytas Bindokas (University of Chicago) and Louie Kerr (Marine Biological Laboratory), Abhishek Kumar, Panagiotis Chandris and Hari Shroff (NIH/NIBIB) for technical support on microscopy; Luke Lavis (Janelia research campus) for Halo dyes and Dibbyendu Bhattacharya (Tata Memorial Center), Sakari Kellokumpu (University of Oulu), Jim Boulter (University of California), Steven Standley (Western University of health sciences) for cDNA constructs used in this study. We thank U of C student, Briana Turner for assistance. The authors declare that they This work was financially supported by NIHRO1 DA035430, DA044760, and DA043361 (W. N. G.) R01 GM104010 (B.S.G.), T32 GM007183 (F.V.) and Peter F. McManus Foundation (W. N. G.). We thank Vytas Bindokas (University of Chicago) and Louie Kerr (Marine Biological Laboratory), Abhishek Kumar, Panagiotis Chandris and Hari Shroff (NIH/NIBIB) for technical support on microscopy; Luke Lavis (Janelia research campus) for Halo dyes and Dibbyendu Bhattacharya (Tata Memorial Center), Sakari Kellokumpu (University of Oulu), Jim Boulter (University of California), Steven Standley (Western University of health sciences) for cDNA constructs used in this study. We thank U of C student, Briana Turner for assistance. The authors declare that they have no competing interests. We especially thank Dr. Karl Matlin for his thorough reading of the manuscript and many insightful comments and suggestions.
ASJC Scopus subject areas
- General Immunology and Microbiology
- General Biochemistry, Genetics and Molecular Biology
- General Neuroscience