Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome

eLife

Fernando M Valbuena¹  Benjamin S Glick¹  Jason C Casler¹  William Ramos²  Abhijit Ramaprasad²  Theron A Russell²  Anitha P Govind²  Luke Newell²  Zola Yi²  Okunola Jeyifous³  William N Green³  Geoffrey T Swanson⁴  Jing-Zhi Yan⁴  Jennifer Lippincott-Schwartz⁵  Aubrey V Weigel⁵ 

[1]Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, United States

[2]Department of Neurobiology, University of Chicago, Chicago, United States

[3]Department of Neurobiology, University of Chicago, Chicago, United States

[4]Marine Biological Laboratory, Woods Hole, United States

[5]Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, United States

[6]Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States

关键词: Golgi;    sialic acid;    glycosylation;    nicotine;    neuronal activity;    Golgi satellites;    Human;    Rat;   

DOI  :  10.7554/eLife.68910

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 that 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 endoplasmic reticulum (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.

【 授权许可】

CC BY