Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome
- University of Chicago, United States
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- The University of Chicago, United States
- Northwestern University, Feinberg School of Medicine, United States
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.
Data availability
Source data files for all quantitative data presented in the current study have been deposited at Dryad. These contain raw data values, statistical summaries, and raw gels for panels in Figs 1, 2, 5, 6, 7, 8, and supplemental figures, figure 1-figure supplement 2, figure 2-figure supplement 2, figure 4-figure supplements 1 and 2, and figure 7-figure supplement 2. The files can be accessed via Dryad (doi:10.5061/dryad.qjq2bvqg3):
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Govind Jeyifous et al eLife manuscript source data filesDryad Digital Repository, doi:10.5061/dryad.qjq2bvqg3.
Article and author information
Author details
Jennifer Lippincott-Schwartz
Funding
National Institutes of Health (DA035430)
- William N Green
National Institutes of Health (DA044760)
- William N Green
National Institutes of Health (DA043361)
- William N Green
National Institutes of Health (GM104010)
- Benjamin S Glick
National Institutes of Health (GM007183)
- Fernando M Valbuena
Peter F McManus Foundation
- William N Green
Howard Hughes Medical Institute
- Jennifer Lippincott-Schwartz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Frederic A Bard, Institute of Molecular and Cell Biology (A*STAR), Singapore
Ethics
Animal experimentation: All animal procedures were approved by the University of Chicago Institutional Animal Care and Use Committee (protocol #72016) and are in accordance with the recommendations of the Panel on Euthanasia of the American Veterinary Medical Association. Strict adherence to AVMA guidelines was followed to prevent pain and suffering of animals.
Version history
- Received: March 30, 2021
- Preprint posted: April 8, 2021 (view preprint)
- Accepted: September 20, 2021
- Accepted Manuscript published: September 21, 2021 (version 1)
- Version of Record published: October 6, 2021 (version 2)
Copyright
© 2021, Govind 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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Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome
eLife 10:e68910.
https://doi.org/10.7554/eLife.68910
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