Slow axonal transport: stop and go traffic in the axon

2000 ◽  
Vol 1 (2) ◽  
pp. 153-156 ◽  
Author(s):  
Anthony Brown
Keyword(s):  
Axonal Transport ◽  
Slow Axonal Transport ◽  
Stop And Go

scholarly journals An exact solution describing slow axonal transport of cytoskeletal elements: the effect of a finite half-life

2012 ◽  
Vol 468 (2147) ◽  
pp. 3384-3397 ◽  
Author(s):  
A. V. Kuznetsov
Keyword(s):  
Exact Solution ◽  
Axonal Transport ◽  
Half Life ◽  
Rectangular Pulse ◽  
Slow Axonal Transport ◽  
Stop And Go ◽  
Cytoskeletal Elements ◽  
The Waves ◽  
State Kinetic ◽  
Two Populations

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

Open Physics ◽  
2012 ◽  
Vol 10 (4) ◽  
Author(s):  
Andrey Kuznetsov
Keyword(s):  
Experimental Data ◽  
Velocity Distribution ◽  
Axonal Transport ◽  
State Model ◽  
Concentration Wave ◽  
Slow Axonal Transport ◽  
Kinesin Motor ◽  
Analytical Expression ◽  
Stop And Go ◽  
Probability Density Function Pdf

AbstractThe 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.

scholarly journals Stochastic Simulation of Neurofilament Transport in Axons: The “Stop-and-Go” Hypothesis

2005 ◽  
Vol 16 (9) ◽  
pp. 4243-4255 ◽  
Author(s):  
Anthony Brown ◽  
Lei Wang ◽  
Peter Jung
Keyword(s):  
Stochastic Model ◽  
Axonal Transport ◽  
Average Velocity ◽  
Cultured Neurons ◽  
Slow Axonal Transport ◽  
Stop And Go ◽  
Kinetics Of ◽  
Fast Rates ◽  
Neurofilament Transport

According to the “stop-and-go” hypothesis of slow axonal transport, cytoskeletal and cytosolic proteins are transported along axons at fast rates but the average velocity is slow because the movements are infrequent and bidirectional. To test whether this hypothesis can explain the kinetics of slow axonal transport in vivo, we have developed a stochastic model of neurofilament transport in axons. We propose that neurofilaments move in both anterograde and retrograde directions along cytoskeletal tracks, alternating between short bouts of rapid movement and short “on-track” pauses, and that they can also temporarily disengage from these tracks, resulting in more prolonged “off-track” pauses. We derive the kinetic parameters of the model from a detailed analysis of the moving and pausing behavior of single neurofilaments in axons of cultured neurons. We show that the model can match the shape, velocity, and spreading of the neurofilament transport waves obtained by radioisotopic pulse labeling in vivo. The model predicts that axonal neurofilaments spend ∼8% of their time on track and ∼97% of their time pausing during their journey along the axon.

Analytical solution of equations describing slow axonal transport based on the stop-and-go hypothesis

Open Physics ◽  
2011 ◽  
Vol 9 (3) ◽  
Author(s):  
Andrey Kuznetsov
Keyword(s):  
Analytical Solution ◽  
Axonal Transport ◽  
Molecular Motor ◽  
Governing Equations ◽  
Slow Axonal Transport ◽  
Stop And Go ◽  
Solution Of Equations ◽  
Physical Insight ◽  
The Difference ◽  
Insight Into

AbstractThis paper presents an analytical solution for slow axonal transport in an axon. The governing equations for slow axonal transport are based on the stop-and-go hypothesis which assumes that organelles alternate between short periods of rapid movement on microtubules (MTs), short on-track pauses, and prolonged off-track pauses, when they temporarily disengage from MTs. The model includes six kinetic states for organelles: two for off-track organelles (anterograde and retrograde), two for running organelles, and two for pausing organelles. An analytical solution is obtained for a steady-state situation. To obtain the analytical solution, the governing equations are uncoupled by using a perturbation method. The solution is validated by comparing it with a high-accuracy numerical solution. Results are presented for neurofilaments (NFs), which are characterized by small diffusivity, and for tubulin oligomers, which are characterized by large diffusivity. The difference in transport modes between these two types of organelles in a short axon is discussed. A comparison between zero-order and first-order approximations makes it possible to obtain a physical insight into the effects of organelle reversals (when organelles change the type of a molecular motor they are attached to, an anterograde versus retrograde motor).

scholarly journals Kinesin Mutations Cause Motor Neuron Disease Phenotypes by Disrupting Fast Axonal Transport in Drosophila

Genetics ◽  
1996 ◽  
Vol 144 (3) ◽  
pp. 1075-1085 ◽  
Author(s):  
Daryl D Hurd ◽  
William M Saxton
Keyword(s):  
Motor Neuron ◽  
Axonal Transport ◽  
Action Potentials ◽  
Light And Electron Microscopy ◽  
Synaptic Membrane ◽  
Slow Axonal Transport ◽  
Fast Axonal Transport ◽  
Motor Neuron Diseases ◽  
Transmitter Secretion ◽  
Axon Terminals

Abstract Previous work has shown that mutation of the gene that encodes the microtubule motor subunit kinesin heavy chain (Khc) in Drosophila inhibits neuronal sodium channel activity, action potentials and neurotransmitter secretion. These physiological defects cause progressive distal paralysis in larvae. To identify the cellular defects that cause these phenotypes, larval nerves were studied by light and electron microscopy. The axons of Khc mutants develop dramatic focal swellings along their lengths. The swellings are packed with fast axonal transport cargoes including vesicles, synaptic membrane proteins, mitochondria and prelysosomal organelles, but not with slow axonal transport cargoes such as cytoskeletal elements. Khc mutations also impair the development of larval motor axon terminals, causing dystrophic morphology and marked reductions in synaptic bouton numbers. These observations suggest that as the concentration of maternally provided wild-type KHC decreases, axonal organelles transported by kinesin periodically stall. This causes organelle jams that disrupt retrograde as well as anterograde fast axonal transport, leading to defective action potentials, dystrophic terminals, reduced transmitter secretion and progressive distal paralysis. These phenotypes parallel the pathologies of some vertebrate motor neuron diseases, including some forms of amyotrophic lateral sclerosis (ALS), and suggest that impaired fast axonal transport is a key element in those diseases.

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