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

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anitha P Govind ◽  
Okunola Jeyifous ◽  
Theron A Russell ◽  
Zola Yi ◽  
Aubrey V Weigel ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Secretory Pathway ◽  
Synapse Formation ◽  
Close Association ◽  
Endocytic Pathway ◽  
Structural Protein ◽  
Functional Changes ◽  
Early Endosomes ◽  
Surface Glycoproteins

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.

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

2021 ◽  
Author(s):  
Anitha P Govind ◽  
Okunola Jeyifous ◽  
Theron A Russell ◽  
Zola Yi ◽  
Aubrey V Weigel ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Secretory Pathway ◽  
Synapse Formation ◽  
Close Association ◽  
Endocytic Pathway ◽  
Structural Protein ◽  
Functional Changes ◽  
Neuronal Excitation ◽  
Early Endosomes ◽  
Surface Glycoproteins

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 excitation. 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 with 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.

scholarly journals Mechanisms of Coupling between Angiotensin Converting Enzyme 2 and Nicotinic Acetylcholine Receptors

2021 ◽  
Author(s):  
Nadine Kabbani ◽  
Kyle Brumfield ◽  
Patricia Sinclair ◽  
Arvind Ramanathan ◽  
Rita Colwell ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Sequence Similarity ◽  
Physical Interaction ◽  
Converting Enzyme ◽  
Structural Protein ◽  
Nicotinic Acetylcholine ◽  
Susceptible Host ◽  
Angiotensin Converting Enzyme 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus encapsulated by a spike (S) glycoprotein envelope, binds with high affinity to angiotensin converting enzyme 2 (ACE2) during cell entry of a susceptible host. Recent studies suggest nicotinic acetylcholine receptors (nAChRs) play a role in functional ACE2 regulation and nicotine may contribute to the progression of coronavirus disease 2019 (COVID-19). Here, we present evidence for coupling between ACE2 and nAChR through bioinformatic analysis and cell culture experiments. Following molecular and structural protein comparison of over 250 ACE2 vertebrate orthologues, a region of human ACE2 at positions C542-L554 was identified to have sequence similarity to nAChR-binding neurotoxin and rabies virus glycoproteins (RBVG). Furthermore, experiments conducted in PC12 cells indicate a potential for physical interaction between ACE2 and alpha 7 nAChR proteins. Our findings support a model of nAChR involvement in in COVID-19.

scholarly journals The Neurophysiological Bases of the Impact of Neonicotinoid Pesticides on the Behaviour of Honeybees

Insects ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 344 ◽  
Author(s):  
Amélie Cabirol ◽  
Albrecht Haase
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Sublethal Effects ◽  
Excitatory Neurotransmitter ◽  
Functional Changes ◽  
Wide Range ◽  
Neonicotinoid Pesticides ◽  
State Of The Science ◽  
The Impact ◽  
Honeybee Brain

Acetylcholine is the main excitatory neurotransmitter in the honeybee brain and controls a wide range of behaviours that ensure the survival of the individuals and of the entire colony. Neonicotinoid pesticides target this neurotransmission pathway and can thereby affect the behaviours under its control, even at doses far below the toxicity limit. These sublethal effects of neonicotinoids on honeybee behaviours were suggested to be partly responsible for the decline in honeybee populations. However, the neural mechanisms by which neonicotinoids influence single behaviours are still unclear. This is mainly due to the heterogeneity of the exposure pathways, doses and durations between studies. Here, we provide a review of the state of the science in this field and highlight knowledge gaps that need to be closed. We describe the agonistic effects of neonicotinoids on neurons expressing the different nicotinic acetylcholine receptors and the resulting brain structural and functional changes, which are likely responsible for the behavioural alterations reported in bees exposed to neonicotinoids.

scholarly journals Endocytic Trafficking Routes of Wild Type and ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator

2004 ◽  
Vol 15 (6) ◽  
pp. 2684-2696 ◽  
Author(s):  
Martina Gentzsch ◽  
Xiu-Bao Chang ◽  
Liying Cui ◽  
Yufeng Wu ◽  
Victor V. Ozols ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Secretory Pathway ◽  
Endocytic Pathway ◽  
Rab Gtpases ◽  
Transmembrane Conductance Regulator ◽  
Wild Type ◽  
Transmembrane Conductance ◽  
Early Endosomes ◽  
Δf508 Cftr ◽  
Cystic Fibrosis Transmembrane

Intracellular trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) is a focus of attention because it is defective in most patients with cystic fibrosis. ΔF508 CFTR, which does not mature conformationally, normally does not exit the endoplasmic reticulum, but if induced to do so at reduced temperature is short-lived at the surface. We used external epitope-tagged constructs to elucidate the itinerary and kinetics of wild type and ΔF508 CFTR in the endocytic pathway and visualized movement of CFTR from the surface to intracellular compartments. Modulation of different endocytic steps with low temperature (16°C) block, protease inhibitors, and overexpression of wild type and mutant Rab GTPases revealed that surface CFTR enters several different routes, including a Rab5-dependent initial step to early endosomes, then either Rab11-dependent recycling back to the surface or Rab7-regulated movement to late endosomes or alternatively Rab9-mediated transit to the trans-Golgi network. Without any of these modulations ΔF508 CFTR rapidly disappears from and does not return to the cell surface, confirming that its altered structure is detected in the distal as well as proximal secretory pathway. Importantly, however, the mutant protein can be rescued at the plasma membrane by Rab11 overexpression, proteasome inhibitors, or inhibition of Rab5-dependent endocytosis.

scholarly journals Glutamatergic Synapse Formation is Promoted by  7-Containing Nicotinic Acetylcholine Receptors

2012 ◽  
Vol 32 (22) ◽  
pp. 7651-7661 ◽  
Author(s):  
A. F. Lozada ◽  
X. Wang ◽  
N. V. Gounko ◽  
K. A. Massey ◽  
J. Duan ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Synapse Formation ◽  
Glutamatergic Synapse ◽  
Nicotinic Acetylcholine

scholarly journals Assessment of the expression and role of the α1-nAChR subunit in efferent cholinergic function during the development of the mammalian cochlea

2016 ◽  
Vol 116 (2) ◽  
pp. 479-492 ◽  
Author(s):  
Isabelle Roux ◽  
Jingjing Sherry Wu (武靜靜) ◽  
J. Michael McIntosh ◽  
Elisabeth Glowatzki
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Synapse Formation ◽  
Mouse Genetics ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Nachr Subunit ◽  
Muscle Type ◽  
Cholinergic Function

Hair cell (HC) activity in the mammalian cochlea is modulated by cholinergic efferent inputs from the brainstem. These inhibitory inputs are mediated by calcium-permeable nicotinic acetylcholine receptors (nAChRs) containing α9- and α10-subunits and by subsequent activation of calcium-dependent potassium channels. Intriguingly, mRNAs of α1- and γ-nAChRs, subunits of the “muscle-type” nAChR have also been found in developing HCs (Cai T, Jen HI, Kang H, Klisch TJ, Zoghbi HY, Groves AK. J Neurosci 35: 5870–5883, 2015; Scheffer D, Sage C, Plazas PV, Huang M, Wedemeyer C, Zhang DS, Chen ZY, Elgoyhen AB, Corey DP, Pingault V. J Neurochem 103: 2651–2664, 2007; Sinkkonen ST, Chai R, Jan TA, Hartman BH, Laske RD, Gahlen F, Sinkkonen W, Cheng AG, Oshima K, Heller S. Sci Rep 1: 26, 2011) prompting proposals that another type of nAChR is present and may be critical during early synaptic development. Mouse genetics, histochemistry, pharmacology, and whole cell recording approaches were combined to test the role of α1-nAChR subunit in HC efferent synapse formation and cholinergic function. The onset of α1-mRNA expression in mouse HCs was found to coincide with the onset of the ACh response and efferent synaptic function. However, in mouse inner hair cells (IHCs) no response to the muscle-type nAChR agonists (±)-anatoxin A, (±)-epibatidine, (−)-nicotine, or 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) was detected, arguing against the presence of an independent functional α1-containing muscle-type nAChR in IHCs. In α1-deficient mice, no obvious change of IHC efferent innervation was detected at embryonic day 18, contrary to the hyperinnervation observed at the neuromuscular junction. Additionally, ACh response and efferent synaptic activity were detectable in α1-deficient IHCs, suggesting that α1 is not necessary for assembly and membrane targeting of nAChRs or for efferent synapse formation in IHCs.

scholarly journals Inhibition of Endosome Function in CHO Cells Bearing a Temperature-sensitive Defect in the Coatomer (COPI) Component ε-COP

1997 ◽  
Vol 139 (7) ◽  
pp. 1747-1759 ◽  
Author(s):  
Elizabeth Daro ◽  
David Sheff ◽  
Marie Gomez ◽  
Thomas Kreis ◽  
Ira Mellman
Keyword(s):  
Mammalian Cells ◽  
Secretory Pathway ◽  
Semliki Forest Virus ◽  
Temperature Shift ◽  
Endocytic Pathway ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Intact Cells ◽  
Early Endosomes ◽  
Mutant Phenotypes

Recent evidence has suggested that subunits of the coatomer protein (COPI) complexes are functionally associated with endosomes in mammalian cells. We now provide genetic evidence that COPI plays a role in endocytosis in intact cells. The ldlF mutant CHO cell line bears a temperature-sensitive defect in the COPI subunit ε-COP. In addition to exhibiting conditional defects in the secretory pathway, we find that the cells are also defective at mediating endosome-associated functions. As found for cells microinjected with anti-COPI antibodies, ldlF cells at the restrictive temperature could not be infected by vesicular stomatitis (VSV) or Semliki Forest virus (SFV) that require delivery to acidic endosomes to penetrate into the cytosol. Although there was no temperature-sensitive defect in the internalization of receptor-bound transferrin (Tfn), Tfn recycling and accumulation of HRP were markedly inhibited at the restrictive temperature. Sorting of receptor-bound markers such as EGF to lysosomes was also reduced, although delivery of fluid-phase markers was only partially inhibited. In addition, lysosomes redistributed from their typical perinuclear location to the tips of the ldlF cells. Mutant phenotypes began to emerge within 2 h of temperature shift, the time required for the loss of detectable ε-COP, suggesting that the endocytic defects were not secondary to a block in the secretory pathway. Importantly, the mutant phenotypes were also corrected by transfection of wild-type ε-COP cDNA demonstrating that they directly or indirectly reflected the ε-COP defect. Taken together, the results suggest that ε-COP acts early in the endocytic pathway, most likely inhibiting the normal sorting and recycling functions of early endosomes.

scholarly journals A Yeast t-SNARE Involved in Endocytosis

1998 ◽  
Vol 9 (10) ◽  
pp. 2873-2889 ◽  
Author(s):  
Karin Séron ◽  
Ville Tieaho ◽  
Cristina Prescianotto-Baschong ◽  
Thomas Aust ◽  
Marie-Odile Blondel ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Secretory Pathway ◽  
Essential Gene ◽  
Specific Interaction ◽  
Endocytic Pathway ◽  
Intracellular Membrane ◽  
Atpase Subunit ◽  
Early Endosomes ◽  
Endocytic Vesicles ◽  
Positively Charged

The ORF YOL018c (TLG2) of Saccharomyces cerevisiae encodes a protein that belongs to the syntaxin protein family. The proteins of this family, t-SNAREs, are present on target organelles and are thought to participate in the specific interaction between vesicles and acceptor membranes in intracellular membrane trafficking. TLG2 is not an essential gene, and its deletion does not cause defects in the secretory pathway. However, its deletion in cells lacking the vacuolar ATPase subunit Vma2p leads to loss of viability, suggesting that Tlg2p is involved in endocytosis. In tlg2Δ cells, internalization was normal for two endocytic markers, the pheromone α-factor and the plasma membrane uracil permease. In contrast, degradation of α-factor and uracil permease was delayed intlg2Δ cells. Internalization of positively charged Nanogold shows that the endocytic pathway is perturbed in the mutant, which accumulates Nanogold in primary endocytic vesicles and shows a greatly reduced complement of early endosomes. These results strongly suggest that Tlg2p is a t-SNARE involved in early endosome biogenesis.

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