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Axonal transport

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https://www.readbyqxmd.com/read/28937869/effect-of-microtubule-disruption-on-dynamics-of-acidic-organelles-in-the-axons-of-primary-cultured-retinal-ganglion-cells
#1
Seiji Miyake, Yuji Takihara, Satoshi Yokota, Yoshihiro Takamura, Masaru Inatani
PURPOSE: Axonal transport is fundamental to autophagy in neuronal cells. To understand its biological significance in various conditions, it is necessary to monitor the process of autophagy. However, monitoring methods are often limited to static analyses, such as protein expression and histological observations. Autophagy has multistep process and is highly dynamic; therefore, additional techniques are necessary to study autophagy. In this study, we quantified the dynamics of autophagy-related organelle transport under conditions of dynamic instability and catastrophic disruption of microtubules using in vitro live imaging...
September 22, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28935671/efa6-regulates-selective-polarised-transport-and-axon-regeneration-from-the-axon-initial-segment
#2
Richard Eva, Hiroaki Koseki, Venkateswarlu Kanamarlapudi, James W Fawcett
Central nervous system (CNS) axons lose their intrinsic ability to regenerate with maturity, whilst peripheral (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their rab11 carriers. We reasoned that exclusion of the contents of rab11 vesicles including integrins might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this using laser axotomy...
September 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28934388/loss-of-slc25a46-causes-neurodegeneration-by-affecting-mitochondrial-dynamics-and-energy-production-in-mice
#3
Zhuo Li, Yanyan Peng, Robert B Hufnagel, Yueh-Chiang Hu, Chuntao Zhao, Luis F Queme, Zaza Khuchua, Ashley M Driver, Fei Dong, Q Richard Lu, Diana M Lindquist, Michael P Jankowski, Rolf W Stottmann, Winston W Y Kao, Taosheng Huang
Recently, we identified biallelic mutations of SLC25A46 in patients with multiple neuropathies. Functional studies revealed that SLC25A46 may play an important role in mitochondrial dynamics by mediating mitochondrial fission. However, the cellular basis and pathogenic mechanism of the SLC25A46-related neuropathies are not fully understood. Thus, we generated a Slc25a46 knock-out mouse model. Mice lacking SLC25A46 displayed severe ataxia, mainly caused by degeneration of Purkinje cells. Increased numbers of small, unmyelinated and degenerated optic nerves as well as loss of retinal ganglion cells indicated optic atrophy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28926622/a-high-mitochondrial-transport-rate-characterizes-cns-neurons-with-high-axonal-regeneration-capacity
#4
Romain Cartoni, Gulcin Pekkurnaz, Chen Wang, Thomas L Schwarz, Zhigang He
Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28926211/kymograph-analysis-with-high-temporal-resolution-reveals-new-features-of-neurofilament-transport-kinetics
#5
J Daniel Fenn, Christopher M Johnson, Juan Peng, Peter Jung, Anthony Brown
We have used kymograph analysis combined with edge detection and an automated computational algorithm to analyze the axonal transport kinetics of neurofilament polymers in cultured neurons at 30 ms temporal resolution. We generated 301 kymographs from 136 movies and analyzed 726 filaments ranging from 0.6 to 42 µm in length, representing ∼37,000 distinct moving and pausing events. We found that the movement is even more intermittent than previously reported and that the filaments undergo frequent, often transient, reversals which suggests that they can engage simultaneously with both anterograde and retrograde motors...
September 19, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28925357/restraint-of-presynaptic-protein-levels-by-wnd-dlk-signaling-mediates-synaptic-defects-associated-with-the-kinesin-3-motor-unc-104
#6
Jiaxing Li, Yao V Zhang, Elham Asghari Adib, Doychin T Stanchev, Xin Xiong, Susan Klinedinst, Pushpanjali Soppina, Thomas Robert Jahn, Richard I Hume, Tobias M Rasse, Catherine A Collins
The kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-104-null mutants are mediated independently of Unc-104's transport function, via the Wallenda (Wnd)/DLK MAP kinase axonal damage signaling pathway. Wnd signaling becomes activated when Unc-104's function is disrupted, and leads to impairment of synaptic structure and function by restraining the expression level of active zone (AZ) and synaptic vesicle (SV) components...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28919207/phospho-regulation-of-soma-to-axon-transcytosis-of-neurotrophin-receptors
#7
Naoya Yamashita, Rajshri Joshi, Sheng Zhang, Zhong-Yin Zhang, Rejji Kuruvilla
Axonal targeting of signaling receptors is essential for neuronal responses to extracellular cues. Here, we report that retrograde signaling by target-derived nerve growth factor (NGF) is necessary for soma-to-axon transcytosis of TrkA receptors in sympathetic neurons, and we define the molecular underpinnings of this positive feedback regulation that enhances neuronal sensitivity to trophic factors. Activated TrkA receptors are retrogradely transported in signaling endosomes from distal axons to cell bodies, where they are inserted on soma surfaces and promote phosphorylation of resident naive receptors, resulting in their internalization...
September 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28918744/intracellular-cargo-transport-by-kinesin-3-motors
#8
REVIEW
N Siddiqui, A Straube
Intracellular transport along microtubules enables cellular cargoes to efficiently reach the extremities of large, eukaryotic cells. While it would take more than 200 years for a small vesicle to diffuse from the cell body to the growing tip of a one-meter long axon, transport by a kinesin allows delivery in one week. It is clear from this example that the evolution of intracellular transport was tightly linked to the development of complex and macroscopic life forms. The human genome encodes 45 kinesins, 8 of those belonging to the family of kinesin-3 organelle transporters that are known to transport a variety of cargoes towards the plus end of microtubules...
July 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28917641/changes-in-innervation-of-lumbar-motoneurons-and-organization-of-premotor-network-following-training-of-transected-adult-rats
#9
Loubna Khalki, Karina Sadlaoud, Julie Lerond, Jacques-Olivier Coq, Jean-Michel Brezun, Laurent Vinay, Patrice Coulon, Hélène Bras
Rats with complete spinal cord transection (SCT) can recover hindlimb locomotor function under strategies combining exercise training and 5-HT agonist treatment. This recovery is expected to result from structural and functional re-organization within the spinal cord below the lesion. To begin to understand the nature of this reorganization, we examined synaptic changes to identified gastrocnemius (GS) or tibialis anterior (TA) motoneurons (MNs) in SCT rats after a schedule of early exercise training and delayed 5-HT agonist treatment...
September 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28912692/calsyntenins-are-expressed-in-a-dynamic-and-partially-overlapping-manner-during-neural-development
#10
Gemma de Ramon Francàs, Tobias Alther, Esther T Stoeckli
Calsyntenins form a family of linker proteins between distinct populations of vesicles and kinesin motors for axonal transport. They were implicated in synapse formation and synaptic plasticity by findings in worms, mice and humans. These findings were in accordance with the postsynaptic localization of the Calsyntenins in the adult brain. However, they also affect the formation of neural circuits, as loss of Calsyntenin-1 (Clstn1) was shown to interfere with axonal branching and axon guidance. Despite the fact that Calsyntenins were discovered originally in embryonic chicken motoneurons, their distribution in the developing nervous system has not been analyzed in detail so far...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28912677/reversible-axonal-dystrophy-by-calcium-modulation-in-frataxin-deficient-sensory-neurons-of-yg8r-mice
#11
Belén Mollá, Diana C Muñoz-Lasso, Fátima Riveiro, Arantxa Bolinches-Amorós, Federico V Pallardó, Angel Fernandez-Vilata, María de la Iglesia-Vaya, Francesc Palau, Pilar Gonzalez-Cabo
Friedreich's ataxia (FRDA) is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG) of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28904207/two-kinesins-drive-anterograde-neuropeptide-transport
#12
Angeline Lim, Andreas Rechtsteiner, William M Saxton
Motor-dependent anterograde transport, a process that moves cytoplasmic components from sites of biosynthesis to sites of use within cells, is crucial in neurons with long axons. Evidence has emerged that multiple anterograde kinesins can contribute to some transport processes. To test the multi-kinesin possibility for a single vesicle type, we studied the functional relationships of axonal kinesins to dense core vesicles (DCVs) that were filled with a GFP-tagged neuropeptide in the Drosophila nervous system...
September 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28904018/dyslipidemia-impairs-mitochondrial-trafficking-and-function-in-sensory-neurons
#13
Amy E Rumora, Stephen I Lentz, Lucy M Hinder, Samuel W Jackson, Andrew Valesano, Gideon E Levinson, Eva L Feldman
Mitochondrial trafficking plays a central role in dorsal root ganglion (DRG) neuronal cell survival and neurotransmission by transporting mitochondria from the neuronal cell body throughout the bundles of DRG axons. In type 2 diabetes (T2DM), dyslipidemia and hyperglycemia damage DRG neurons and induce mitochondrial dysfunction; however, the impact of free fatty acids and glucose on mitochondrial trafficking in DRG neurons remains unknown. To evaluate the impact of free fatty acids compared to hyperglycemia on mitochondrial transport, primary adult mouse DRG neuron cultures were treated with physiologic concentrations of palmitate and glucose and assessed for alterations in mitochondrial trafficking, mitochondrial membrane potential, and mitochondrial bioenergetics...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28894417/myosin-v-induces-cargo-immobilization-and-clustering-at-the-axon-initial-segment
#14
Anne F J Janssen, Roderick P Tas, Petra van Bergeijk, Rosalie Oost, Casper C Hoogenraad, Lukas C Kapitein
The selective transport of different cargoes into axons and dendrites underlies the polarized organization of the neuron. Although it has become clear that the combined activity of different motors determines the destination and selectivity of transport, little is known about the mechanistic details of motor cooperation. For example, the exact role of myosin-V in opposing microtubule-based axon entries has remained unclear. Here we use two orthogonal chemically-induced heterodimerization systems to independently recruit different motors to cargoes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28891525/hodgkin-huxley-model-based-on-ionic-transport-in-axoplasmic-fluid
#15
Suman Bhatia, Phool Singh, Prabha Sharma
Hodgkin-Huxley model has been reframed to incorporate the physical parameters of fluid inside the axon. The reframed model comprises of set of partial differential equations containing the physical parameters: density, mass fraction of sodium, potassium and chlorine ions, longitudinal diffusivity of ions and rate of additions of ions along with the temperature. Obtained conduction velocity of 19.5m/sec at a temperature of 18.5 degree celcius and conduction velocity dependency on temperature within the range 5 to 25 degree celcius are two important results that strongly validate the proposed model...
2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/28883787/investigations-into-hypoxia-and-oxidative-stress-at-the-optic-nerve-head-in-a-rat-model-of-glaucoma
#16
Glyn Chidlow, John P M Wood, Robert J Casson
The vascular hypothesis of glaucoma proposes that retinal ganglion cell axons traversing the optic nerve head (ONH) undergo oxygen and nutrient insufficiency as a result of compromised local blood flow, ultimately leading to their degeneration. To date, evidence for the hypothesis is largely circumstantial. Herein, we made use of an induced rat model of glaucoma that features reproducible and widespread axonal transport disruption at the ONH following chronic elevation of intraocular pressure. If vascular insufficiency plays a role in the observed axonal transport failure, there should exist a physical signature at this time point...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28882840/influence-of-a-gsk3%C3%AE-phosphorylation-site-within-the-proximal-c-terminus-of-neurofilament-h-on-neurofilament-dynamics
#17
Rishel Brenna Vohnoutka, Edward F Boumil, Yuguan Liu, Atsuko Uchida, Harish C Pant, Thomas B Shea
Phosphorylation of the C-terminal tail of the heavy neurofilament subunit (NF-H) impacts NF axonal transport and residence within axons by fostering NF-NF associations that compete with transport. We tested the role of phosphorylation of a GSK-3β consensus site (S493) located in the proximal portion of the NF-H tail, in NF dynamics by transfection of NB2a/d1 cells with NF-H where S493 was mutated to aspartic acid (S493D) or to alanine (S493A) to mimic constitutive phosphorylation and non-phosphorylation. S493D underwent increased transport into axonal neurites, while S493A displayed increased perikaryal NF aggregates that were decorated by anti-kinesin...
September 7, 2017: Biology Open
https://www.readbyqxmd.com/read/28882593/real-time-subpixel-accuracy-tracking-of-single-mitochondria-in-neurons-reveals-heterogeneous-mitochondrial-motion
#18
Adolfo Alsina, Wu Ming Lai, Wai Kin Wong, Xianan Qin, Min Zhang, Hyokeun Park
Mitochondria are essential for cellular survival and function. In neurons, mitochondria are transported to various subcellular regions as needed. Thus, defects in the axonal transport of mitochondria are related to the pathogenesis of neurodegenerative diseases, and the movement of mitochondria has been the subject of intense research. However, the inability to accurately track mitochondria with subpixel accuracy has hindered this research. Here, we report an automated method for tracking mitochondria based on the center of fluorescence...
September 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28882303/digital-quantification-of-neurite-outgrowth-and-retraction-by-phase-contrast-microscopy-a-tau-perspective
#19
Brett Cook, Duncan Proctor, Rachel Bromberg, Nichole E LaPointe, Stuart C Feinstein, Leslie Wilson
The proper organization and function of the mammalian nervous system relies on neuronal processes or "neurites," extended morphological projections that include axons and dendrites. Tau is a structural microtubule-associated protein that is widely expressed in the nervous system that mediates the establishment of cell polarity, neurite outgrowth, and axonal transport. A useful model for studying the establishment and maintenance of these neuronal structures are rat neuronal PC12 cells, which can be induced to express tau and project neurites by treating the cells with nerve growth factor...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28882299/single-molecule-imaging-of-tau-dynamics-on-the-microtubule-surface
#20
Jamie L Stern, Dominique V Lessard, Rehan Ali, Christopher L Berger
The microtubule-associated protein Tau is primarily expressed in neurons and plays an integral role in the regulation of multiple functions within the axon. In the adult brain, the six Tau isoforms are expressed allowing for a complex system of control. Despite Tau's central role, the mechanisms by which Tau acts are not fully understood. We have used single-molecule total internal reflection fluorescence (TIRF) microscopy and the methods described in this chapter to further our knowledge of Tau's behavior and function...
2017: Methods in Cell Biology
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