The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
A V Kuznetsov - One of the best experts on this subject based on the ideXlab platform.
-
a coupled model of fast Axonal Transport of organelles and Slow Axonal Transport of tau protein
Computer Methods in Biomechanics and Biomedical Engineering, 2015Co-Authors: I A Kuznetsov, A V KuznetsovAbstract:We have developed a model that accounts for the effect of a non-uniform distribution of tau protein along the axon length on fast Axonal Transport of intracellular organelles. The tau distribution is simulated by using a Slow Axonal Transport model; the numerically predicted tau distributions along the axon length were validated by comparing them with experimentally measured tau distributions reported in the literature. We then developed a fast Axonal Transport model for organelles that accounts for the reduction of kinesin attachment rate to microtubules by tau. We investigated organelle Transport for two situations: (1) a uniform tau distribution and (2) a non-uniform tau distribution predicted by the Slow Axonal Transport model. We found that non-uniform tau distributions observed in healthy axons (an increase in tau concentration towards the axon tip) result in a significant enhancement of organelle Transport towards the synapse compared with the uniform tau distribution with the same average amount o...
-
an exact solution of transient equations describing Slow Axonal Transport
Computer Methods in Biomechanics and Biomedical Engineering, 2013Co-Authors: A V KuznetsovAbstract:An exact analytical solution of equations describing Slow Axonal Transport of cytoskeletal elements (CEs) injected in an axon is presented. The equations modelling Slow Axonal Transport are based on the stop-and-go hypothesis. The simplest model implementing this hypothesis postulates that CEs switch between pausing and running kinetic states, and that the probabilities of CE transition between these two states are described by first-order rate constants. It is assumed that initially CEs are injected such that they form a uniform pulse of a given width. All injected CEs are initially attributed to the pausing state. It is shown that within 30 s kinetic processes redistribute CEs between pausing and running states; after that the process occurs under quasi-equilibrium conditions. The parameter accessible to experiments is the total concentration of CEs (pausing plus running). As the initial rectangular-shaped pulse moves, it changes its shape to become a bell-shaped wave that spreads out as it propagates. ...
-
an exact solution describing Slow Axonal Transport of cytoskeletal elements the effect of a finite half life
Proceedings of The Royal Society A: Mathematical Physical and Engineering Sciences, 2012Co-Authors: A V KuznetsovAbstract:This paper presents an exact solution for a two kinetic state model of Slow Axonal Transport that is based on the stop-and-go hypothesis. The model accounts for two populations of cytoskeletal elements (CEs): pausing and running. The model also accounts for a finite half-life of CEs involved in Slow Axonal Transport. It is assumed that initially CEs are injected into the axon such that their concentration forms a rectangular pulse; initially all CEs are assumed to be in the pausing state. Kinetic processes quickly redistribute CEs between the pausing and running states. After less than a minute, equilibrium is established, forming two pulses, representing concentrations of pausing and running CEs, respectively. As these pulses propagate, their shape changes and they turn to bell-shaped waves. The amplitude of the waves decreases, and the waves spread out as they propagate down the axon. The rate of the amplitude decrease is larger for CEs with a shorter half-life, but even if CE half-life is infinitely long, some decrease of the waves' amplitudes is observed. The velocity of the waves' propagation is found to be independent of the CE half-life and is in good agreement with published experimental data for Slow Axonal Transport of neurofilaments.
-
effect of kinesin velocity distribution on Slow Axonal Transport
Central European Journal of Physics, 2012Co-Authors: A V KuznetsovAbstract:The goal of this paper is to investigate the effect that a distribution of kinesin motor velocities could have on cytoskeletal element (CE) concentration waves in Slow Axonal Transport. Previous models of Slow Axonal Transport based on the stop-and-go hypothesis (P. Jung, A. Brown, Modeling the Slowing of neurofilament Transport along the mouse sciatic nerve, Physical Biology 6 (2009) 046002) assumed that in the anterograde running state all CEs move with one and the same velocity as they are propelled by kinesin motors. This paper extends the aforementioned theoretical approach by allowing for a distribution of kinesin motor velocities; the distribution is described by a probability density function (PDF). For a two kinetic state model (that accounts for the pausing and running populations of CEs) an analytical solution describing the propagation of the CE concentration wave is derived. Published experimental data are used to obtain an analytical expression for the PDF characterizing the kinesin velocity distribution; this analytical expression is then utilized as an input for computations. It is demonstrated that accounting for the kinesin velocity distribution increases the rate of spreading of the CE concentration waves, which is a significant improvement in the two kinetic state model.
-
investigation of the role of diffusivity on spreading rate and merging of the bell shaped waves in Slow Axonal Transport
International Journal for Numerical Methods in Biomedical Engineering, 2011Co-Authors: A V Kuznetsov, A A Avramenko, D G BlinovAbstract:This paper investigates the role of diffusivity on spreading, rate, and merging of two waves Transporting the same type of cytoskeletal elements (CEs) in Slow Axonal Transport. The two waves (each wave physically represents the total probability density function for the CEs) can be generated by simultaneous microinjections of radiolabeled CEs in two different locations. Alternatively, two waves, one behind another, can be produced by injecting CEs at the same location twice, with a time interval between the injections. Since the waves become wider as they propagate downstream, the two waves eventually merge; this results in the formation of a single wave that moves down the axon. The amplitudes of the waves (before as well as after they merge) decrease as the waves propagate downstream; in addition, the waves spread out during their propagation. The waves spread out faster when diffusivity of free CEs is increased; this agrees with experimental data for the Transport of neurofilaments, which are characterized by smaller diffusivity, versus Transport of tubulin oligomers, which are characterized by larger diffusivity. The average velocity of CE Transport first increases (which is explained by the effect of the initial condition; this effect is somewhat artificial) and then attains an asymptotic value. The case of merging of three waves is also briefly investigated. Copyright © 2010 John Wiley & Sons, Ltd.
D G Blinov - One of the best experts on this subject based on the ideXlab platform.
-
investigation of the role of diffusivity on spreading rate and merging of the bell shaped waves in Slow Axonal Transport
International Journal for Numerical Methods in Biomedical Engineering, 2011Co-Authors: A V Kuznetsov, A A Avramenko, D G BlinovAbstract:This paper investigates the role of diffusivity on spreading, rate, and merging of two waves Transporting the same type of cytoskeletal elements (CEs) in Slow Axonal Transport. The two waves (each wave physically represents the total probability density function for the CEs) can be generated by simultaneous microinjections of radiolabeled CEs in two different locations. Alternatively, two waves, one behind another, can be produced by injecting CEs at the same location twice, with a time interval between the injections. Since the waves become wider as they propagate downstream, the two waves eventually merge; this results in the formation of a single wave that moves down the axon. The amplitudes of the waves (before as well as after they merge) decrease as the waves propagate downstream; in addition, the waves spread out during their propagation. The waves spread out faster when diffusivity of free CEs is increased; this agrees with experimental data for the Transport of neurofilaments, which are characterized by smaller diffusivity, versus Transport of tubulin oligomers, which are characterized by larger diffusivity. The average velocity of CE Transport first increases (which is explained by the effect of the initial condition; this effect is somewhat artificial) and then attains an asymptotic value. The case of merging of three waves is also briefly investigated. Copyright © 2010 John Wiley & Sons, Ltd.
-
modeling traffic jams in Slow Axonal Transport
Journal of Mechanics in Medicine and Biology, 2010Co-Authors: A V Kuznetsov, A A Avramenko, D G BlinovAbstract:The purpose of this paper is to develop a model capable of simulating traffic jams in Slow Axonal Transport. Slowing of Slow Axonal Transport is an early sign of some neurodegenerative diseases. Axonal swellings observed near the end stage of such diseases may be an indication of traffic jams developing in axons that cause the Slowing down of Slow Axonal Transport. Traffic jams may result from misregulation of microtubule-associated proteins caused by an imbalance in intracellular signaling or by mutations of these proteins. This misregulation leads to a decay of microtubule tracks in axons, effectively reducing the number of "railway tracks" available for molecular-motor-assisted Transport of intracellular organelles. In this paper, the decay of microtubule tracks is modeled by a reduction of the number density of microtubules in the central part of the axon. Simulation results indicate that the model predicts the build-up of the bell-shaped concentration wave, as the wave approaches the bottleneck (blockage) region. This increase in concentration will likely plug the bottleneck region resulting in a traffic jam that would hinder the Slow Axonal Transport.
-
effect of diffusion on Slowing the velocity of a bell shaped wave in Slow Axonal Transport
International Communications in Heat and Mass Transfer, 2010Co-Authors: A V Kuznetsov, A A Avramenko, D G BlinovAbstract:Abstract This paper models Transport of organelles by Slow Axonal Transport utilizing the stop-and-go hypothesis, which postulates that in Slow Axonal Transport the motion of organelles does not occur continuously; instead, organelles move along microtubules (MTs) alternating between short periods of rapid movement, short on-track pauses, and prolonged off-track pauses, when they temporarily disengage from MTs. The model considers six kinetic states of organelles: anterogradely moving state, retrogradely moving state, anterogradely pausing state, retrogradely pausing state, off-track anterograde state, and off-track retrograde state. The paper extends the existing model of Slow Axonal Transport by accounting for the diffusivity of off-track organelles and investigates how the diffusivity of these organelles affects the amplitude, velocity, and rate of change of the variance of the bell-shaped wave which describes the probability density function (PDF) corresponding to the ratio of the chance of finding an organelle within an infinitesimal interval in the axon to the length of this interval. The velocity of this wave characterizes the average effective velocity (calculated including pauses) of an organelle in Slow Axonal Transport while the rate of change of the variance characterizes the rate of spread of the initial packet of organelles Transported in the axon. The goal of this research is not only to develop a more accurate Transport model, but also to understand fundamentally the effects of diffusion on Slow Axonal Transport. It is demonstrated that diffusion decreases the amplitude of the wave and increases the rate of its spread but does not affect wave's velocity.
-
effect of protein degradation in the axon on the speed of the bell shaped concentration wave in Slow Axonal Transport
International Communications in Heat and Mass Transfer, 2009Co-Authors: A V Kuznetsov, A A Avramenko, D G BlinovAbstract:This paper investigates the effect of degradation of proteins Transported by means of Slow Axonal Transport (due to enzyme-mediated breakdown of proteins) on the speed of the bell-shaped wave of protein concentration propagating toward the synapse of the axon. Another issue investigated in this paper is the effect of protein degradation on the traffic jam caused by a decay of microtubule tracks at a certain location in the axon. The decay of microtubule tracks may be caused by misregulation of microtubule-associated proteins resulting from an imbalance in intracellular signaling or by mutations of these proteins. Axonal swellings caused by such traffic jams hinder Axonal Transport; they are a likely cause of various neurodegenerative diseases, including Alzheimer's and Parkinson's diseases and the Down syndrome.
-
macroscopic modeling of Slow Axonal Transport of rapidly diffusible soluble proteins
International Communications in Heat and Mass Transfer, 2009Co-Authors: A V Kuznetsov, A A Avramenko, D G BlinovAbstract:Abstract The purpose of this paper is to develop a macroscopic model of Slow Axonal Transport of soluble proteins which may be Transported in axons by both diffusion and active molecular-motor-assisted Transport mechanisms. The model relies on the “stop-and-go” hypothesis put forward by Brown et al. [A. Brown, L. Wang, P. Jung, Stochastic simulation of neurofilament Transport in axons: the “stop-and-go” hypothesis, Molecular Biology of the Cell 16 (2005) 4243–4255.] according to which the motion of neurofilaments in Slow Axonal Transport does not occur at a constant velocity; instead, neurofilaments move along microtubules alternating between short periods of rapid movement, short on-track pauses, and prolonged off-track pauses, when they temporarily disengage from microtubules. For soluble proteins, diffusion may also play an important role in overall Slow Axonal Transport; to account for this effect governing equations of the dynamic system model developed in Craciun et al. [G. Craciun, A. Brown, A. Friedman, A dynamical system model of neurofilament in axons, Journal of Theoretical Biology 237 (2005) 316–322.] are extended to incorporate diffusivity of off track proteins (proteins unbound to a stationary matrix). The model correctly predicts that the total concentration of organelles forms the bell-shaped wave that spreads out as it propagates toward the axon tip.
Yoshiaki Komiya - One of the best experts on this subject based on the ideXlab platform.
-
cilostazol prevents impairment of Slow Axonal Transport in streptozotocin diabetic rats
European Journal of Pharmacology, 2000Co-Authors: Yoshinobu Yasuda, Yasuchika Yamamoto, Yoshiaki KomiyaAbstract:Abstract We studied the effects of cilostazol, an antiplatelet and vasodilating agent, on Axonal Transport patterns of cytoskeletal proteins in the motor fibers of sciatic nerve of streptozotocin-induced diabetic rats. Proteins labeled with l -[ 35 S]methionine in 6-mm consecutive segments of the nerve were analyzed electrophoretically following fractionation into Triton-soluble and-insoluble subpopulations. Transport rates of proteins (particularly neurofilaments) in Slow component a were reduced by 50% 2 weeks after labeling (4 weeks after streptozotocin). An apparent reduction of tubulin and actin was observed at later intervals after induction of diabetes. Actin Transported in Slow component b was also impaired, though to a lesser extent than in component a. Cilostazol prevented Transport impairment of both Slow components a and b without affecting hyperglycemia or reduction in body weight gain. These results suggest that in sciatic motor fibers early defects in Slowly Transported proteins are more marked in Slow component a, and that impairment may be caused primarily by hemodynamic abnormalities.
-
Impairment of Cytoskeletal Protein Transport due to Aging or ββ’-lminodipropionitrile Intoxication in the Rat Sciatic Nerve
Gerontology, 1994Co-Authors: Tomoko Tashiro, Yoshiaki KomiyaAbstract:Three major age-related changes in cytoskeletal organization and metabolism in the axon were observed by comparing Slow Axonal Transport in the sciatic nerves of rats aged 7-80 weeks: (a) a progressiv
-
Axonal Transport of actin and actin-binding proteins in the rat sciatic nerve
Neuroscience Research, 1994Co-Authors: Kiyoshi Tanaka, Sumito Sekimoto, Tomoko Tashiro, Yoshiaki KomiyaAbstract:Abstract Actin is one of the major cytoskeletal proteins carried in Slow Axonal Transport. Since more than 50% of actin in the axon was recovered in the high-speed supernatant, we looked for G-actin-binding proteins in Slow Axonal Transport. Two weeks after injection of l -[ 35 S]methionine into the rat spinal cord (L 3 –L 5 ), labeled proteins in the sciatic nerve were extracted and those with potential abilities to interact with G-actin were detected by two independent methods: (A) DNAase I affinity chromatography and (B) blot overlay with biotinylated actin. By method (A), a 68 kDa Ca 2+ -dependent binding protein and a 45 kDa Ca 2+ -independent binding protein were detected. The 68 kDa protein was also a major protein binding to actin in method (B). The 68 kDa protein was identified with the Ca 2+ -dependent phospholipid binding protein annexin VI by two-dimensional electrophoresis and Western blotting. As annexin VI is a component of Slow Axonal Transport, it does not seem to be bound to membranous organelles in the axon. Our results suggest that annexin VI may play a role in the control of actin assembly and membrane-microfilament interaction.
-
organization and Slow Axonal Transport of cytoskeletal proteins under normal and regenerating conditions
Molecular Neurobiology, 1992Co-Authors: Tomoko Tashiro, Yoshiaki KomiyaAbstract:The organization of the Axonal cytoskeleton was investigated by analyzing the solubility and Transport profile of the major cytoskeletal proteins in motor axons of the rat sciatic nerve under normal and regenerating conditions. When extracted with the Triton-containing buffer at low temperature, 50% of tubulin and 30% of actin were recovered in the insoluble form resistant to further depolymerizing treatments. Most of this cold-insoluble form was Transported in Slow component a (SCa), the Slower of the two subcomponents of Slow Axonal Transport, whereas the cold-soluble form showed a biphasic distribution between SCa and SCb (Slow component b).
-
two 68 kda proteins in Slow Axonal Transport belong to the 70 kda heat shock protein family and the annexin family
Journal of Neurochemistry, 1991Co-Authors: Sumito Sekimoto, Tomoko Tashiro, Yoshiaki KomiyaAbstract:: The major 68-kDa protein found selectively in the faster of the two subcomponents of Slow Axonal Transport [group IV or Slow component b (SCb)] in the rat sciatic nerve has been characterized. It was found to contain two distinct classes of proteins, S1 and S2, both of which have isoelectric points of 5.7, but differ in their solubility in the presence of calcium. The S1 protein, which contributes up to 70% of the 68-kDa component, was soluble in the presence or absence of calcium, whereas the S2 protein was bound to the cytoskeleton in a calcium-dependent manner. Further characterization of the two proteins by peptide mapping and immunological methods revealed that the S1 protein belonged to a family of proteins related to the 70-kDa heat shock protein, whereas the S2 protein was identical to 68-kDa calelec-trin (annexin VI). Selective occurrence in SCb of these proteins with potential abilities to regulate protein-protein or protein-membrane interactions suggests that they may play important roles in the control of cytoskeletal organization in the axon, because SCb contains mainly cytoskeletal proteins in a more dynamic form compared with the Slowest rate component, Slow component a, which is enriched in the stably polymerized form of these proteins.
Sumio Terada - One of the best experts on this subject based on the ideXlab platform.
-
kinesin 1 hsc70 dependent mechanism of Slow Axonal Transport and its relation to fast Axonal Transport
Biophysical Journal, 2011Co-Authors: Sumio Terada, Masataka Kinjo, Makoto Aihara, Yosuke Takei, Nobutaka HirokawaAbstract:Cytoplasmic protein Transport in axons (‘Slow Axonal Transport’) is essential for neuronal homeostasis, and involves Kinesin-1, the same motor for membranous organelle Transport (‘fast Axonal Transport’). However, both molecular mechanisms of Slow Axonal Transport and difference in usage of Kinesin-1 between Slow and fast Axonal Transport have been elusive. Here, we show that Slow Axonal Transport depends on the interaction between the DnaJ-like domain of the kinesin light chain in the Kinesin-1 motor complex and Hsc70, scaffolding between cytoplasmic proteins and Kinesin-1. The domain is within the tetratricopeptide repeat, which can bind to membranous organelles, and competitive perturbation of the domain in squid giant axons disrupted cytoplasmic protein Transport and reinforced membranous organelle Transport, indicating that this domain might have a function as a switchover system between Slow and fast Transport by Hsc70. Transgenic mice overexpressing a dominant-negative form of the domain showed delayed Slow Transport, accelerated fast Transport and optic axonopathy without elevation of intraocular pressure. These findings provide a basis for the regulatory mechanism of intracellular Transport and its intriguing implication in the understanding of neuronal dysfunction such as normal tension glaucoma.View Large Image | View Hi-Res Image | Download PowerPoint Slide
-
kinesin 1 hsc70 dependent mechanism of Slow Axonal Transport and its relation to fast Axonal Transport
The EMBO Journal, 2010Co-Authors: Sumio Terada, Masataka Kinjo, Makoto Aihara, Yosuke Takei, Nobutaka HirokawaAbstract:Cytoplasmic protein Transport in axons (‘Slow Axonal Transport’) is essential for neuronal homeostasis, and involves Kinesin‐1, the same motor for membranous organelle Transport (‘fast Axonal Transport’). However, both molecular mechanisms of Slow Axonal Transport and difference in usage of Kinesin‐1 between Slow and fast Axonal Transport have been elusive. Here, we show that Slow Axonal Transport depends on the interaction between the DnaJ‐like domain of the kinesin light chain in the Kinesin‐1 motor complex and Hsc70, scaffolding between cytoplasmic proteins and Kinesin‐1. The domain is within the tetratricopeptide repeat, which can bind to membranous organelles, and competitive perturbation of the domain in squid giant axons disrupted cytoplasmic protein Transport and reinforced membranous organelle Transport, indicating that this domain might have a function as a switchover system between Slow and fast Transport by Hsc70. Transgenic mice overexpressing a dominant‐negative form of the domain showed delayed Slow Transport, accelerated fast Transport and optic axonopathy. These findings provide a basis for the regulatory mechanism of intracellular Transport and its intriguing implication in neuronal dysfunction.
-
where does Slow Axonal Transport go
Neuroscience Research, 2003Co-Authors: Sumio TeradaAbstract:Axonal Transport is the specialized and well-developed intracellular Transport system for regulated and/or long-distance Transport based on generalized cellular machineries. Among them, Slow Axonal Transport conveys cytoplasmic proteins. The motor molecule, the nature of Transporting complex and the Transport regulation mechanism for Slow Transport are still unclarified. There has been a dispute regarding the nature of Transporting complex of cytoskeletal proteins, polymer-sliding hypothesis versus subunit-Transport theory. Recent data supporting the hypothesis of polymer sliding in cultured neurons only reconfirm the previously reported structure and this inference suffers from the lack of ultrastructural evidence and the direct relevance to the physiological Slow Transport phenomenon in vivo. Observation of the moving cytoskeletal proteins in vivo using transgenic mice or squid giant axons revealed that subunits do move in a microtubule-dependent manner, strongly indicating the involvement of microtubule-based motor kinesin. If the Slow Transport rate reflects the intermittent fast Transport dependent on kinesin motor, we have to investigate the molecular constituents of the Transporting complex in more detail and evaluate why the motor and cargo interaction is so unstable. This kind of weak and fluctuating interaction between various molecular pairs could not be detected by conventional techniques, thus necessitating the establishment of a new experimental system before approaching the molecular regulation problem.
-
visualization of Slow Axonal Transport in vivo
Science, 1996Co-Authors: Sumio Terada, Takao Nakata, Alan C Peterson, Nobutaka HirokawaAbstract:In axons, cytoskeletal constituents move by Slow Transport. However, it remains controversial whether Axonal neurofilaments are dynamic structures in which only subunits are Transported or whether filaments assemble in the proximal axon and are Transported intact as polymers to the axon terminus. To investigate the form neurofilament proteins take during Transport, neurons of transgenic mice lacking Axonal neurofilaments were infected with a recombinant adenoviral vector encoding epitope-tagged neurofilament M. Confocal and electron microscopy revealed that the virally encoded neurofilament M was Transported in unpolymerized form along Axonal microtubules. Thus, neurofilament proteins are probably Transported as subunits or small oligomers along microtubules, which are major routes for Slow Axonal Transport.
Nobutaka Hirokawa - One of the best experts on this subject based on the ideXlab platform.
-
kinesin 1 hsc70 dependent mechanism of Slow Axonal Transport and its relation to fast Axonal Transport
Biophysical Journal, 2011Co-Authors: Sumio Terada, Masataka Kinjo, Makoto Aihara, Yosuke Takei, Nobutaka HirokawaAbstract:Cytoplasmic protein Transport in axons (‘Slow Axonal Transport’) is essential for neuronal homeostasis, and involves Kinesin-1, the same motor for membranous organelle Transport (‘fast Axonal Transport’). However, both molecular mechanisms of Slow Axonal Transport and difference in usage of Kinesin-1 between Slow and fast Axonal Transport have been elusive. Here, we show that Slow Axonal Transport depends on the interaction between the DnaJ-like domain of the kinesin light chain in the Kinesin-1 motor complex and Hsc70, scaffolding between cytoplasmic proteins and Kinesin-1. The domain is within the tetratricopeptide repeat, which can bind to membranous organelles, and competitive perturbation of the domain in squid giant axons disrupted cytoplasmic protein Transport and reinforced membranous organelle Transport, indicating that this domain might have a function as a switchover system between Slow and fast Transport by Hsc70. Transgenic mice overexpressing a dominant-negative form of the domain showed delayed Slow Transport, accelerated fast Transport and optic axonopathy without elevation of intraocular pressure. These findings provide a basis for the regulatory mechanism of intracellular Transport and its intriguing implication in the understanding of neuronal dysfunction such as normal tension glaucoma.View Large Image | View Hi-Res Image | Download PowerPoint Slide
-
kinesin 1 hsc70 dependent mechanism of Slow Axonal Transport and its relation to fast Axonal Transport
The EMBO Journal, 2010Co-Authors: Sumio Terada, Masataka Kinjo, Makoto Aihara, Yosuke Takei, Nobutaka HirokawaAbstract:Cytoplasmic protein Transport in axons (‘Slow Axonal Transport’) is essential for neuronal homeostasis, and involves Kinesin‐1, the same motor for membranous organelle Transport (‘fast Axonal Transport’). However, both molecular mechanisms of Slow Axonal Transport and difference in usage of Kinesin‐1 between Slow and fast Axonal Transport have been elusive. Here, we show that Slow Axonal Transport depends on the interaction between the DnaJ‐like domain of the kinesin light chain in the Kinesin‐1 motor complex and Hsc70, scaffolding between cytoplasmic proteins and Kinesin‐1. The domain is within the tetratricopeptide repeat, which can bind to membranous organelles, and competitive perturbation of the domain in squid giant axons disrupted cytoplasmic protein Transport and reinforced membranous organelle Transport, indicating that this domain might have a function as a switchover system between Slow and fast Transport by Hsc70. Transgenic mice overexpressing a dominant‐negative form of the domain showed delayed Slow Transport, accelerated fast Transport and optic axonopathy. These findings provide a basis for the regulatory mechanism of intracellular Transport and its intriguing implication in neuronal dysfunction.
-
Slow Axonal Transport: the subunit Transport model
Trends in Cell Biology, 1997Co-Authors: Nobutaka Hirokawa, Sumio Teradatakeshi Funakoshi, Sen TakedaAbstract:A central problem concerning Slow Transport of cytoskeletal proteins along nerve axons is where they are assembled and the form in which they are Transported. The polymer and subunit Transport models are the two major hypotheses. Recent developments using molecular and cellular biophysics, molecular cell biology and gene technology have enabled visualization of moving forms of cytoskeletal proteins during their Transport. Here, we argue that these studies support the subunit Transport theory.
-
visualization of Slow Axonal Transport in vivo
Science, 1996Co-Authors: Sumio Terada, Takao Nakata, Alan C Peterson, Nobutaka HirokawaAbstract:In axons, cytoskeletal constituents move by Slow Transport. However, it remains controversial whether Axonal neurofilaments are dynamic structures in which only subunits are Transported or whether filaments assemble in the proximal axon and are Transported intact as polymers to the axon terminus. To investigate the form neurofilament proteins take during Transport, neurons of transgenic mice lacking Axonal neurofilaments were infected with a recombinant adenoviral vector encoding epitope-tagged neurofilament M. Confocal and electron microscopy revealed that the virally encoded neurofilament M was Transported in unpolymerized form along Axonal microtubules. Thus, neurofilament proteins are probably Transported as subunits or small oligomers along microtubules, which are major routes for Slow Axonal Transport.