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Axonal transport

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https://www.readbyqxmd.com/read/29475137/polarized-trafficking-the-palmitoylation-cycle-distributes-cytoplasmic-proteins-to-distinct-neuronal-compartments
#1
REVIEW
Elena Tortosa, Casper C Hoogenraad
In neurons, polarized cargo distribution occurs mainly between the soma and axonal and dendritic compartments, and requires coordinated regulation of cytoskeletal remodeling and membrane trafficking. The Golgi complex plays a critical role during neuronal polarization and secretory trafficking has been shown to differentially transport proteins to both axons and dendrites. Besides the Golgi protein sorting, recent data revealed that palmitoylation cycles are an efficient mechanism to localize cytoplasmic, non-transmembrane proteins to particular neuronal compartments, such as the newly formed axon...
February 20, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29473915/infection-and-transport-of-herpes-simplex-virus-type-1-in-neurons-role-of-the-cytoskeleton
#2
REVIEW
Monica Miranda-Saksena, Christopher E Denes, Russell J Diefenbach, Anthony L Cunningham
Herpes simplex virus type 1 (HSV-1) is a neuroinvasive human pathogen that has the ability to infect and replicate within epithelial cells and neurons and establish a life-long latent infection in sensory neurons. HSV-1 depends on the host cellular cytoskeleton for entry, replication, and exit. Therefore, HSV-1 has adapted mechanisms to promote its survival by exploiting the microtubule and actin cytoskeletons to direct its active transport, infection, and spread between neurons and epithelial cells during primary and recurrent infections...
February 23, 2018: Viruses
https://www.readbyqxmd.com/read/29470488/intracellular-amyloid-beta-expression-leads-to-dysregulation-of-the-mitogen-activated-protein-kinase-and-bone-morphogenetic-protein-2-signaling-axis
#3
Eric Cruz, Sushil Kumar, Li Yuan, Jyothi Arikkath, Surinder K Batra
Alzheimer's disease (AD) is a neurodegenerative syndrome classically depicted by the parenchymal accumulation of extracellular amyloid beta plaques. However, recent findings suggest intraneuronal amyloid beta (iAβ1-42) accumulation precedes extracellular deposition. Furthermore, the pathologic increase in iAβ1-42 has been implicated in dysregulation of cellular mechanisms critically important in axonal transport. Owing to neuronal cell polarity, retrograde and anterograde axonal transport are essential trafficking mechanism necessary to convey membrane bound neurotransmitters, neurotrophins, and endosomes between soma and synaptic interfaces...
2018: PloS One
https://www.readbyqxmd.com/read/29468294/behavioral-phenotyping-and-dopamine-dynamics-in-mice-with-conditional-deletion-of-the-glutamate-transporter-glt-1-in-neurons-resistance-to-the-acute-locomotor-effects-of-amphetamine
#4
Kathryn D Fischer, Alex C W Houston, Rajeev I Desai, Michelle R Doyle, Jack Bergman, Maha Mian, Rebekah Mannix, David L Sulzer, Se Joon Choi, Eugene V Mosharov, Nathaniel W Hodgson, Anita Bechtholt, Klaus A Miczek, Paul A Rosenberg
RATIONALE: GLT-1 is the major glutamate transporter in the brain and is expressed predominantly in astrocytes but is also present in excitatory axon terminals. To understand the functional significance of GLT-1 expressed in neurons, we generated a conditional GLT-1 knockout mouse and inactivated GLT-1 in neurons using Cre-recombinase expressed under the synapsin 1 promoter, (synGLT-1 KO). OBJECTIVES: Abnormalities of glutamate homeostasis have been shown to affect hippocampal-related behaviors including learning and memory as well as responses to drugs of abuse...
February 22, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29468178/retrograde-interferon-gamma-signaling-induces-major-histocompatibility-class-i-expression-in-human-induced-pluripotent-stem-cell-derived-neurons
#5
Benjamin D S Clarkson, Misha S Patel, Reghann G LaFrance-Corey, Charles L Howe
Objective: Injury-associated axon-intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN γ ) signals are known to induce expression of major histocompatibility class I (MHC I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen-specific CD8+ T cells. We sought to determine whether the same is true in human neurons...
February 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29467617/quantitative-proteomics-of-synaptosomal-fractions-in-a-rat-overexpressing-human-disc1-gene-indicates-profound-synaptic-dysregulation-in-the-dorsal-striatum
#6
Fernando J Sialana, An-Li Wang, Benedetta Fazari, Martina Kristofova, Roman Smidak, Svenja V Trossbach, Carsten Korth, Joseph P Huston, Maria A de Souza Silva, Gert Lubec
Disrupted-in-schizophrenia 1 (DISC1) is a key protein involved in behavioral processes and various mental disorders, including schizophrenia and major depression. A transgenic rat overexpressing non-mutant human DISC1, modeling aberrant proteostasis of the DISC1 protein, displays behavioral, biochemical and anatomical deficits consistent with aspects of mental disorders, including changes in the dorsal striatum, an anatomical region critical in the development of behavioral disorders. Herein, dorsal striatum of 10 transgenic DISC1 (tgDISC1) and 10 wild type (WT) littermate control rats was used for synaptosomal preparations and for performing liquid chromatography-tandem mass spectrometry (LC-MS)-based quantitative proteomics, using isobaric labeling (TMT10plex)...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29467464/loss-of-the-drosophila-m-aaa-mitochondrial-protease-paraplegin-results-in-mitochondrial-dysfunction-shortened-lifespan-and-neuronal-and-muscular-degeneration
#7
Gautam Pareek, Ruth E Thomas, Leo J Pallanck
The progressive accumulation of dysfunctional mitochondria is implicated in aging and in common diseases of the elderly. To oppose this occurrence, organisms employ a variety of strategies, including the selective degradation of oxidatively damaged and misfolded mitochondrial proteins. Genetic studies in yeast indicate that the ATPase Associated with diverse cellular Activities (AAA+ ) family of mitochondrial proteases account for a substantial fraction of this protein degradation, but their metazoan counterparts have been little studied, despite the fact that mutations in the genes encoding these proteases cause a variety of human diseases...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29465329/the-time-course-of-ongoing-activity-during-neuritis-and-following-axonal-transport-disruption
#8
Ieva Satkeviciute, George Goodwin, Geoffrey M Bove, Andrew Dilley
Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons, and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS, but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or non-inflammatory axonal transport disruption...
February 21, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29463867/optogenetic-tractography-for-anatomo-functional-characterization-of-cortico-subcortical-neural-circuits-in-non-human-primates
#9
S Senova, C Poupon, J Dauguet, H J Stewart, G P Dugué, C Jan, K Hosomi, G S Ralph, L Barnes, X Drouot, C Pouzat, J F Mangin, F Pain, I Doignon, R Aron-Badin, E Brouillet, E S Boyden, K A Mitrophanous, P Hantraye, S Palfi
Dissecting neural circuitry in non-human primates (NHP) is crucial to identify potential neuromodulation anatomical targets for the treatment of pharmacoresistant neuropsychiatric diseases by electrical neuromodulation. How targets of deep brain stimulation (DBS) and cortical targets of transcranial magnetic stimulation (TMS) compare and might complement one another is an important question. Combining optogenetics and tractography may enable anatomo-functional characterization of large brain cortico-subcortical neural pathways...
February 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29462701/quantitative-comparison-of-vesicular-glutamate-transporters-in-rat-deep-cerebellar-nuclei
#10
Haian Mao, Salah Hamodeh, Fahad Sultan
The excitatory synapses of the rat deep cerebellar nuclei (DCN) were quantitatively analyzed by vesicular glutamate transporter 1 and 2 (vGluT1 and vGluT2) immunolabeling. We calculated the number and sizes of the labelled boutons and compared them between lateral /dentate nucleus (LN/DN), posterior interposed nucleus (PIN), anterior interposed nucleus (AIN), and medial nucleus (MN). The density of vGluT1+ boutons differs significantly within these nuclei. In contrast, the vGluT2+ bouton density is more similar between different nuclei...
February 17, 2018: Neuroscience
https://www.readbyqxmd.com/read/29462608/mrnp-assembly-axonal-transport-and-local-translation-in-neurodegenerative-diseases
#11
Bilal Khalil, Dmytro Morderer, Phillip L Price, Feilin Liu, Wilfried Rossoll
The development, maturation, and maintenance of the mammalian nervous system rely on complex spatiotemporal patterns of gene expression. In neurons, this is achieved by the expression of differentially localized isoforms and specific sets of mRNA-binding proteins (mRBPs) that regulate RNA processing, mRNA trafficking, and local protein synthesis at remote sites within dendrites and axons. There is growing evidence that axons contain a specialized transcriptome and are endowed with the machinery that allows them to rapidly alter their local proteome via local translation and protein degradation...
February 17, 2018: Brain Research
https://www.readbyqxmd.com/read/29451229/m-aaa-proteases-mitochondrial-calcium-homeostasis-and-neurodegeneration
#12
REVIEW
Maria Patron, Hans-Georg Sprenger, Thomas Langer
The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected...
February 16, 2018: Cell Research
https://www.readbyqxmd.com/read/29448966/exosomes-taken-up-by-neurons-hijack-the-endosomal-pathway-to-spread-to-interconnected-neurons
#13
Juan Carlos Polanco, Chuanzhou Li, Nela Durisic, Robert Sullivan, Jürgen Götz
In Alzheimer disease and related disorders, the microtubule-associated protein tau aggregates and forms cytoplasmic lesions that impair neuronal physiology at many levels. In addition to affecting the host neuron, tau aggregates also spread to neighboring, recipient cells where the misfolded tau aggregates, in a manner similar to prions, actively corrupt the proper folding of soluble tau, and thereby impair cellular functions. One vehicle for the transmission of tau aggregates are secretory nanovesicles known as exosomes...
February 15, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29446228/integrins-promote-axonal-regeneration-after-injury-of-the-nervous-system
#14
Bart Nieuwenhuis, Barbara Haenzi, Melissa R Andrews, Joost Verhaagen, James W Fawcett
Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling...
February 15, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29445117/transitional-correlation-between-inner-membrane-potential-and-atp-levels-of-neuronal-mitochondria
#15
R Suzuki, K Hotta, K Oka
The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMP mito ), and little is known about the dynamics of native mitochondrial ATP (ATP mito ). This study conducted simultaneous imaging of IMP mito and ATP mito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29436751/nigrostriatal-dopamine-transporter-availability-in-early-parkinson-s-disease
#16
Patrik Fazio, Per Svenningsson, Zsolt Cselényi, Christer Halldin, Lars Farde, Andrea Varrone
BACKGROUND: The imaging of biomarkers for characterization of dopaminergic impairment in Parkinson's disease (PD) is useful for diagnosis, patient stratification, and assessment of treatment outcomes. [ 18 F]FE-PE2I is an improved imaging tool allowing for detailed mapping of the dopamine transporter protein in the nigro-striatal system at the level of cell bodies (substantia nigra), axons, and presynaptic terminals (striatum). OBJECTIVES: The objective of this study was to compare the dopamine transporter protein loss in the presynaptic terminals to that in the cell bodies and axons in early PD patients using [ 18 F](E)-N-(3-iodoprop-2-enyl)-2b-carbofluoroethoxy-3b-(4'-methyl-phenyl) nortropane ([ 18 F]FE-PE2I) and high-resolution PET...
February 13, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29434374/reactive-oxygen-species-regulate-axonal-regeneration-through-the-release-of-exosomal-nadph-oxidase-2-complexes-into-injured-axons
#17
Arnau Hervera, Francesco De Virgiliis, Ilaria Palmisano, Luming Zhou, Elena Tantardini, Guiping Kong, Thomas Hutson, Matt C Danzi, Rotem Ben-Tov Perry, Celio X C Santos, Alexander N Kapustin, Roland A Fleck, José Antonio Del Río, Thomas Carroll, Vance Lemmon, John L Bixby, Ajay M Shah, Mike Fainzilber, Simone Di Giovanni
Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis...
February 12, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29431653/regulation-of-synapse-development-by-vgat-deletion-from-erbb4-positive-interneurons
#18
Thiri W Lin, Zhibing Tan, Arnab Barik, Dong-Min Yin, Egil Brudvik, Hongsheng Wang, Wen-Cheng Xiong, Lin Mei
GABA signaling has been implicated in neural development; however, in vivo genetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied synapse development by ablating vesicular GABA transporter Vgat in in ErbB4-positive (ErbB4+) interneurons. We show that inhibitory axo-somatic synapses onto pyramidal neurons vary from one cortical layer to another; however, inhibitory synapses on axon initial segments (AISs) were similar across layers. On the other hand, PV-positive (PV+)/ErbB4+ interneurons and PV-only interneurons receive a higher number of inhibitory synapses from PV+ErbB4+ interneurons, compared with ErbB4-only interneurons...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29430519/heterogeneities-in-axonal-structure-and-transporter-distribution-lower-dopamine-reuptake-efficiency
#19
Cihan Kaya, Mary H Cheng, Ethan R Block, Tom M Bartol, Terrence J Sejnowski, Alexander Sorkin, James R Faeder, Ivet Bahar
Efficient clearance of dopamine (DA) from the synapse is key to regulating dopaminergic signaling. This role is fulfilled by DA transporters (DATs). Recent advances in the structural characterization of DAT from Drosophila (dDAT) and in high-resolution imaging of DA neurons and the distribution of DATs in living cells now permit us to gain a mechanistic understanding of DA reuptake events in silico. Using electron microscopy images and immunofluorescence of transgenic knock-in mouse brains that express hemagglutinin-tagged DAT in DA neurons, we reconstructed a realistic environment for MCell simulations of DA reuptake, wherein the identity, population and kinetics of homology-modeled human DAT (hDAT) substates were derived from molecular simulations...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29427758/screen-for-slit-robo-signaling-in-trunk-neural-cells-reveals-new-players
#20
Darwin Martinez, Nora Zuhdi, Michelle Reyes, Blanca Ortega, Dion Giovannone, Vivian Lee, Maria Elena de Bellard
Slits ligands and their Robo receptors are involved in quite disparate cell signaling pathways that include axon guidance, cell proliferation, cell motility and angiogenesis. Neural crest cells emerge by delamination from neural cells in the dorsal neural tube, and give rise to various components of the peripheral nervous system in vertebrates. It is well established that these cells change from a non-migratory to a highly migratory state allowing them to reach distant regions before they differentiate. However, but the mechanism controlling this delamination and subsequent migration are still not fully understood...
February 7, 2018: Gene Expression Patterns: GEP
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