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

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Govind, A. P., Jeyifous, O., Russell, T. A., Yi, Z., Weigel, A., Ramaprasad, A., Newell, L., Ramos, W., Valbuena, F. M., Casler, J. C., Yan, J.-Z., Glick, B. S., Swanson, G. T., Lippincott-Schwartz, J., & Green, W. N. Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome. Elife, 10, (2021): e68910, https://doi.org/10.7554/eLife.68910.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.This work was financially supported by NIH RO1 DA035430, DA044760, and DA043361 (WNG) R01 GM104010 (BSG), T32 GM007183 (FV), and Peter F McManus Foundation (WNG)

Utility of IOLMaster 700 Swept-Source Optical Coherence Tomography in Detecting Macular Disease for Preoperative Cataract Surgery Patients

PurposeTo assess the efficacy of IOLMaster 700 (IOLM) biometer swept-source optical coherence tomography (SS-OCT) in detecting macular pathology before cataract surgery and to compare IOLM SS-OCT characteristics of foveal pathology with a widely used spectral-domain OCT (SD-OCT) system.Patients and methodsRetrospective analysis of 1156 consecutive eyes with IOLMaster 700 SS-OCT undergoing cataract surgery from January to June 2017 was performed. Approximately a third of these eyes (327 eyes) also had a SD-OCT scan performed previously. A single reviewer assessed each SS-OCT scan and identified them as "normal" or "abnormal." SS-OCT sensitivity and specificity in identifying foveal pathology was assessed using findings on Spectralis SD-OCT scans as the gold standard.ResultsOf 327 eyes with both IOLM SS-OCT and Spectralis SD-OCT scans, 121 eyes (37.0%) had abnormal SS-OCT scans. Of these 121 eyes, SD-OCT scans confirmed pathology in 104 eyes (86.0%). Of the remaining 206 eyes graded to have normal SS-OCT scans, 84 eyes (40.8%) had normal SD-OCT scans, and 122 eyes (59.2%) had pathologic findings on SD-OCT scans. For each pathologic condition, subtle but definitive differences existed in the appearance of the IOLM SS-OCT and SD-OCT images.ConclusionUsing a normal or abnormal Spectralis SD-OCT scan as confirmation of absence or presence of foveal pathology respectively, we found a high positive predictive value (86.0%) of an abnormal IOLM SS-OCT scan and a high specificity (83.2%) but low sensitivity (46.0%) and negative predictive value (40.8%) of a normal-appearing SS-OCT scan. These results suggest that an abnormal IOLM SS-OCT scan in an eye without known pathology is a strong indicator of an abnormal macula and should prompt further evaluation of the retina to identify pathology prior to cataract surgery. Importantly, IOLM SS-OCT scans do not detect all macular pathology and cannot be used as a screening test for identifying macular pathology

Prevalence and Knowledge of Potential Interactions Between Over-the-Counter Products and Apixaban.

BackgroundDirect-acting oral anticoagulants (DOACs), such as apixaban, are the most commonly prescribed anticoagulants, with advantages in that they do not require routine monitoring. However, less frequent contact with healthcare professionals may contribute to poor patient knowledge about potential interactions between over-the-counter (OTC) products and DOACs.ObjectiveDetermine the prevalence of use of OTC products (OTC medications and dietary supplements) with potentially serious apixaban interactions and assess patient knowledge of potential interactions.DesignCross-sectional survey.SettingAcademic-affiliated outpatient medical practices in northern and southern California.ParticipantsA total of 791 English- or Spanish-speaking patients prescribed apixaban.MeasurementsUse and knowledge of OTC medications and dietary supplements with potentially serious apixaban interactions.ResultsAlmost all respondents (n = 771; 97.5%) reported OTC product use. Of respondents, 33% (n = 266) took at least one OTC product with potentially serious apixaban interactions daily/most days and 53 (6.7%) took multiple products (mean = 2.6 [SD = 2.6]). Aspirin was taken daily by 116 (14.7%; of which 75 [64.7%] also consumed other potentially interacting OTC products), and some days/as needed by an additional 82 (10.4%). Ibuprofen and naproxen were taken daily/most days by 14 (1.8%) and occasionally by 225 (28.5%). Dietary supplements with potentially serious interactions were taken daily/most days by 160 (20.2%). Approximately 66% of respondents were either uncertain or incorrect about the potential for increased bleeding from combining nonsteroidal anti-inflammatory drugs and apixaban. Less knowledge about OTC products with potentially serious interactions was associated with greater OTC product use (odds ratio = 0.54; 95% confidence interval = 0.35-0.85).ConclusionSignificant numbers of patients take OTC products (particularly dietary supplements) with potentially serious interactions with the DOAC apixaban and appear to lack knowledge about potentially harmful interactions. Interventions are needed to educate patients and healthcare providers about potential dangers of taking interacting OTC products in combination with apixaban, and data are needed on outcomes associated with concomitant apixaban-OTC product use. J Am Geriatr Soc 68:155-162, 2019

Prevalence and Knowledge of Potential Interactions Between Over‐the‐Counter Products and Apixaban

BackgroundDirect-acting oral anticoagulants (DOACs), such as apixaban, are the most commonly prescribed anticoagulants, with advantages in that they do not require routine monitoring. However, less frequent contact with healthcare professionals may contribute to poor patient knowledge about potential interactions between over-the-counter (OTC) products and DOACs.ObjectiveDetermine the prevalence of use of OTC products (OTC medications and dietary supplements) with potentially serious apixaban interactions and assess patient knowledge of potential interactions.DesignCross-sectional survey.SettingAcademic-affiliated outpatient medical practices in northern and southern California.ParticipantsA total of 791 English- or Spanish-speaking patients prescribed apixaban.MeasurementsUse and knowledge of OTC medications and dietary supplements with potentially serious apixaban interactions.ResultsAlmost all respondents (n = 771; 97.5%) reported OTC product use. Of respondents, 33% (n = 266) took at least one OTC product with potentially serious apixaban interactions daily/most days and 53 (6.7%) took multiple products (mean = 2.6 [SD = 2.6]). Aspirin was taken daily by 116 (14.7%; of which 75 [64.7%] also consumed other potentially interacting OTC products), and some days/as needed by an additional 82 (10.4%). Ibuprofen and naproxen were taken daily/most days by 14 (1.8%) and occasionally by 225 (28.5%). Dietary supplements with potentially serious interactions were taken daily/most days by 160 (20.2%). Approximately 66% of respondents were either uncertain or incorrect about the potential for increased bleeding from combining nonsteroidal anti-inflammatory drugs and apixaban. Less knowledge about OTC products with potentially serious interactions was associated with greater OTC product use (odds ratio = 0.54; 95% confidence interval = 0.35-0.85).ConclusionSignificant numbers of patients take OTC products (particularly dietary supplements) with potentially serious interactions with the DOAC apixaban and appear to lack knowledge about potentially harmful interactions. Interventions are needed to educate patients and healthcare providers about potential dangers of taking interacting OTC products in combination with apixaban, and data are needed on outcomes associated with concomitant apixaban-OTC product use. J Am Geriatr Soc 68:155-162, 2019

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

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