Yan Jing-Zhi

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Yan
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Jing-Zhi
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  • Article
    Selective and regulated trapping of nicotinic receptor weak base ligands and relevance to smoking cessation
    (eLife, 2017-07-18) Govind, Anitha P. ; Vallejo, Yolanda F. ; Stolz, Jacob R. ; Yan, Jing-Zhi ; Swanson, Geoffrey T. ; Green, William N.
    To better understand smoking cessation, we examined the actions of varenicline (Chantix) during long-term nicotine exposure. Varenicline reduced nicotine upregulation of α4β2-type nicotinic receptors (α4β2Rs) in live cells and neurons, but not for membrane preparations. Effects on upregulation depended on intracellular pH homeostasis and were not observed if acidic pH in intracellular compartments was neutralized. Varenicline was trapped as a weak base in acidic compartments and slowly released, blocking 125I-epibatidine binding and desensitizing α4β2Rs. Epibatidine itself was trapped; 125I-epibatidine slow release from acidic vesicles was directly measured and required the presence of α4β2Rs. Nicotine exposure increased epibatidine trapping by increasing the numbers of acidic vesicles containing α4β2Rs. We conclude that varenicline as a smoking cessation agent differs from nicotine through trapping in α4β2R-containing acidic vesicles that is selective and nicotine-regulated. Our results provide a new paradigm for how smoking cessation occurs and suggest how more effective smoking cessation reagents can be designed.
  • Article
    Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome
    (eLife Sciences Publications, 2021-09-21) Govind, Anitha P. ; Jeyifous, Okunola ; Russell, Theron A. ; Yi, Zola ; Weigel, Aubrey V. ; Ramaprasad, Abhijit ; Newell, Luke ; Ramos, William ; Valbuena, Fernando M. ; Casler, Jason C. ; Yan, Jing-Zhi ; Glick, Benjamin S. ; Swanson, Geoffrey T. ; Lippincott-Schwartz, Jennifer ; Green, William N.
    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.