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Lipid membrane interactions neurons

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https://www.readbyqxmd.com/read/29644863/reversible-cation-selective-attachment-and-self-assembly-of-human-tau-on-supported-brain-lipid-membranes
#1
Stefania A Mari, Susanne Wegmann, Katharina Tepper, Bradley Hyman, Eva-Maria Mandelkow, Eckhard Mandelkow, Daniel J Müller
Misfolding and aggregation of the neuronal, microtubule associated protein tau is involved in the pathogenesis of Alzheimer's disease and tauopathies. It has been proposed that neuronal membranes could play a role in tau release, internalization and aggregation, and that tau aggregates could exert toxicity via membrane permeabilization. Whether and how tau interacts with lipid membranes remains a matter of discussion. Here, we characterize the interaction of full-length human tau (htau40) with supported lipid membranes (SLMs) made from brain total lipid extract by time-lapse high-resolution atomic force microscopy (AFM)...
April 12, 2018: Nano Letters
https://www.readbyqxmd.com/read/29604406/interaction-of-dynamin-i-with-nap-22-a-neuronal-protein-enriched-in-the-presynaptic-region
#2
Satoko Ueno, Hiroshi Miyoshi, Yoko Maruyama, Mitsuhiro Morita, Shohei Maekawa
Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant low-density membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM and localizes in the presynaptic region. In order to know the role of NAP-22 in the synaptic transmission, NAP-22 binding proteins in the cytosol were searched with an affinity screening with NAP-22 as a bait and several protein bands were detected. Using mass-analysis and western blotting, one of the main band of ∼90 kDa was identified as dynamin I...
March 28, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29580771/interactions-of-amyloid-%C3%AE-peptides-on-lipid-bilayer-studied-by-single-molecule-imaging-and-tracking
#3
Chun-Chieh Chang, Elin Edwald, Sarah Veatch, Duncan G Steel, Ari Gafni
The amyloid-β peptides (Aβ40 and Aβ42) feature prominently in the synaptic dysfunction and neuronal loss associated with Alzheimer's disease (AD). This has been proposed to be due either to interactions between Aβ and cell surface receptors affecting cell signaling, or to the formation of calcium-permeable channels in the membrane that disrupt calcium homeostasis. In both mechanisms the cell membrane is the primary cellular structure with which Aβ interacts. Aβ concentrations in human bodily fluids are very low (pM-nM) rendering studies of the size, composition, cellular binding sites and mechanism of action of the oligomers formed in vivo very challenging...
March 23, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29559883/estrogen-interactions-with-lipid-rafts-related-to-neuroprotection-impact-of-brain-ageing-and-menopause
#4
REVIEW
Raquel Marin, Mario Diaz
Estrogens (E2) exert a plethora of neuroprotective actions against aged-associated brain diseases, including Alzheimer's disease (AD). Part of these actions takes place through binding to estrogen receptors (ER) embedded in signalosomes, where numerous signaling proteins are clustered. Signalosomes are preferentially located in lipid rafts which are dynamic membrane microstructures characterized by a peculiar lipid composition enriched in gangliosides, saturated fatty acids, cholesterol, and sphingolipids. Rapid E2 interactions with ER-related signalosomes appear to trigger intracellular signaling ultimately leading to the activation of molecular mechanisms against AD...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29551631/vdac1-mitochondrial-dysfunction-and-alzheimer-s-disease
#5
REVIEW
Varda Shoshan-Barmatz, Edna Nahon-Crystal, Anna Shteinfer-Kuzmine, Rajeev Gupta
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis...
March 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29526709/cause-and-consequence-of-a%C3%AE-lipid-interactions-in-alzheimer-disease-pathogenesis
#6
REVIEW
Vijayaraghavan Rangachari, Dexter N Dean, Pratip Rana, Ashwin Vaidya, Preetam Ghosh
Self-templating propagation of protein aggregate conformations is increasingly becoming a significant factor in many neurological diseases. In Alzheimer disease (AD), intrinsically disordered amyloid-β (Aβ) peptides undergo aggregation that is sensitive to environmental conditions. High-molecular weight aggregates of Aβ that form insoluble fibrils are deposited as senile plaques in AD brains. However, low-molecular weight aggregates called soluble oligomers are known to be the primary toxic agents responsible for neuronal dysfunction...
March 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29524645/inhibitory-effect-of-several-sphingolipid-metabolites-on-calcineurin
#7
Yoko Maruyama, Satoko Ueno, Mitsuhiro Morita, Fumio Hayashi, Shohei Maekawa
Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM. In a previous study, we showed that DRM-derived NAP-22 binds ganglioside and the inhibitory effect of ganglioside to calcineurin (CaN), a neuron-enriched calmodulin-regulated phosphoprotein phosphatase. Considering the important roles of CaN in neurons, identification of other cellular regulators of CaN could be a good clue to understand the molecular background of neuronal function...
March 7, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29514050/mechanism-of-aggregation-and-membrane-interactions-of-mammalian-prion-protein
#8
REVIEW
Ambadi Thody Sabareesan, M K Mathew, Jayant B Udgaonkar
The cellular prion protein (PrPC ), which is present ubiquitously in all mammalian neurons, is normally found to be linked to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. The conformational conversion of PrPC into misfolded and aggregated forms is associated with transmissible neurodegenerative diseases known as prion diseases. The importance of different misfolded conformations in prion diseases, and the mechanism by which prion aggregates induce neurotoxicity remain poorly understood...
March 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29491369/endoplasmic-reticulum-and-mitochondria-in-diseases-of-motor-and-sensory-neurons-a-broken-relationship
#9
REVIEW
Nathalie Bernard-Marissal, Roman Chrast, Bernard L Schneider
Recent progress in the understanding of neurodegenerative diseases revealed that multiple molecular mechanisms contribute to pathological changes in neurons. A large fraction of these alterations can be linked to dysfunction in the endoplasmic reticulum (ER) and mitochondria, affecting metabolism and secretion of lipids and proteins, calcium homeostasis, and energy production. Remarkably, these organelles are interacting with each other at specialized domains on the ER called mitochondria-associated membranes (MAMs)...
February 28, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29474891/regulation-of-kv7-2-kv7-3-channels-by-cholesterol-relevance-of-an-optimum-plasma-membrane-cholesterol-content
#10
Mayra Delgado-Ramírez, Sergio Sánchez-Armass, Ulises Meza, Aldo A Rodríguez-Menchaca
Kv7.2/Kv7.3 channels are the molecular correlate of the M-current, which stabilizes the membrane potential and controls neuronal excitability. Previous studies have shown the relevance of plasma membrane lipids on both M-currents and Kv7.2/Kv7.3 channels. Here, we report the sensitive modulation of Kv7.2/Kv7.3 channels by membrane cholesterol level. Kv7.2/Kv7.3 channels transiently expressed in HEK-293 cells were significantly inhibited by decreasing the cholesterol level in the plasma membrane by three different pharmacological strategies: methyl-β-cyclodextrin (MβCD), Filipin III, and cholesterol oxidase treatment...
February 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29428500/electrostatic-and-hydrophobic-interactions-of-lipid-associated-%C3%AE-synuclein-the-role-of-a-water-limited-interfaces-in-amyloid-fibrillation
#11
REVIEW
Tae Su Choi, Jong Yoon Han, Chae Eun Heo, Sun Woo Lee, Hugh I Kim
Human α‑synuclein (αSyn) is an intrinsically disordered protein (IDP) whose biological and pathological functions in brain neuronal cells have not yet been fully elucidated. αSyn intrinsically participates in aiding neurotransmitter trafficking through αSyn the association with lipid membranes. However, lipid-associated states of αSyn also induce amyloid self-assembly that is linked to the pathogenesis of various synucleinopathies. These contradicting actions arise from the limited water content near lipid-water interfaces that controls αSyn electrostatic and hydrophobic interactions...
February 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29408451/fluorescence-imaging-of-the-interaction-of-amyloid-beta-40-peptides-with-lives-cells-and-model-membrane
#12
Elaheh Jamasbi, Mohammed Akhter Hossain, Masha Tan, Frances Separovic, Giuseppe D Ciccotosto
Amyloid beta peptides (Aβ) found in plaques in the brain have been widely recognised as a hallmark of Alzheimer's disease although the underlying mechanism is still unknown. Aβ40 and Aβ40(A2T) peptides were synthesized and their effects on neuronal cells are reported together with the effect of tetramer forms of the peptides. ThT assay revealed that mutation affected the lag time and aggregation and the presence of lipid vesicles changed the fibril formation profile for both peptides. The A2T mutation appeared to reduce cytotoxicity and lessen binding of Aβ40 peptides to neuronal cells...
February 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29386468/simulation-study-on-complex-conformations-of-a%C3%AE-42-peptides-on-a-gm1-ganglioside-containing-lipid-membrane
#13
Majid Vahed, Saburo Neya, Katsumi Matsuzaki, Tyuji Hoshino
Aggregation and complex formation of amyloid beta (Aβ) peptides on a neuronal cell membrane is a hallmark of neuro-disturbance diseases. In this work, we performed molecular dynamics (MD) simulations to investigate the initial stage of interactions of multiple Aβ42 peptides on a GM1 ganglioside-containing membrane that mimics a micro-domain on the neuronal cell surface. Conformational changes of Aβs due to adhesion on the membrane and subsequent molecular interactions among the Aβs were monitored. It was suggested from results of the two 1...
2018: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29364242/in-vivo-single-molecule-tracking-at-the-drosophila-presynaptic-motor-nerve-terminal
#14
Adekunle T Bademosi, Elsa Lauwers, Rumelo Amor, Patrik Verstreken, Bruno van Swinderen, Frédéric A Meunier
An increasing number of super-resolution microscopy techniques are helping to uncover the mechanisms that govern the nanoscale cellular world. Single-molecule imaging is gaining momentum as it provides exceptional access to the visualization of individual molecules in living cells. Here, we describe a technique that we developed to perform single-particle tracking photo-activated localization microscopy (sptPALM) in Drosophila larvae. Synaptic communication relies on key presynaptic proteins that act by docking, priming, and promoting the fusion of neurotransmitter-containing vesicles with the plasma membrane...
January 14, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29347346/elucidating-distinct-ion-channel-populations-on-the-surface-of-hippocampal-neurons-via-single-particle-tracking-recurrence-analysis
#15
Grzegorz Sikora, Agnieszka Wyłomańska, Janusz Gajda, Laura Solé, Elizabeth J Akin, Michael M Tamkun, Diego Krapf
Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface...
December 2017: Physical Review. E
https://www.readbyqxmd.com/read/29242346/structural-basis-of-membrane-disruption-and-cellular-toxicity-by-%C3%AE-synuclein-oligomers
#16
Giuliana Fusco, Serene W Chen, Philip T F Williamson, Roberta Cascella, Michele Perni, James A Jarvis, Cristina Cecchi, Michele Vendruscolo, Fabrizio Chiti, Nunilo Cremades, Liming Ying, Christopher M Dobson, Alfonso De Simone
Oligomeric species populated during the aggregation process of α-synuclein have been linked to neuronal impairment in Parkinson's disease and related neurodegenerative disorders. By using solution and solid-state nuclear magnetic resonance techniques in conjunction with other structural methods, we identified the fundamental characteristics that enable toxic α-synuclein oligomers to perturb biological membranes and disrupt cellular function; these include a highly lipophilic element that promotes strong membrane interactions and a structured region that inserts into lipid bilayers and disrupts their integrity...
December 15, 2017: Science
https://www.readbyqxmd.com/read/29236684/cryo-em-structures-of-the-tmem16a-calcium-activated-chloride-channel
#17
Shangyu Dang, Shengjie Feng, Jason Tien, Christian J Peters, David Bulkley, Marco Lolicato, Jianhua Zhao, Kathrin Zuberbühler, Wenlei Ye, Lijun Qi, Tingxu Chen, Charles S Craik, Yuh Nung Jan, Daniel L Minor, Yifan Cheng, Lily Yeh Jan
Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy...
December 21, 2017: Nature
https://www.readbyqxmd.com/read/29234100/a-bi-fluorescence-complementation-system-to-detect-associations-between-the-endoplasmic-reticulum-and-mitochondria
#18
Mark Harmon, Philip Larkman, Giles Hardingham, Mandy Jackson, Paul Skehel
Close contacts between the endoplasmic reticulum membrane and the mitochondrial outer membrane facilitate efficient transfer of lipids between the organelles and coordinate Ca2+ signalling and stress responses. Changes to this coupling is associated with a number of metabolic disorders and neurodegenerative diseases including Alzheimer's, Parkinson's and motor neuron disease. The distance between the two membranes at regions of close apposition is below the resolution of conventional light microscopy, which makes analysis of these interactions challenging...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196683/preferential-selection-of-arginine-at-the-lipid-water-interface-of-trpv1-during-vertebrate-evolution-correlates-with-its-snorkeling-behaviour-and-cholesterol-interaction
#19
Somdatta Saha, Arijit Ghosh, Nikhil Tiwari, Ashutosh Kumar, Abhishek Kumar, Chandan Goswami
TRPV1 is a thermo-sensitive ion channel involved in neurosensory and other physiological functions. The trans-membrane helices of TRPV1 undergo quick and complex conformational changes governed by thermodynamic parameters and membrane components leading to channel opening. However, the molecular mechanisms underlying such events are poorly understood. Here we analysed the molecular evolution of TRPV1 at the lipid-water-interface region (LWI), typically defined as a layer of 6 Å thickness on each side of the membrane with less availability of free water...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158482/structural-basis-for-the-unique-ganglioside-and-cell-membrane-recognition-mechanism-of-botulinum-neurotoxin-dc
#20
Sicai Zhang, Ronnie P-A Berntsson, William H Tepp, Liang Tao, Eric A Johnson, Pål Stenmark, Min Dong
Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides...
November 21, 2017: Nature Communications
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