P3-258 Molecular motors implicated in the fast axonal transport of tau

2004 ◽  
Vol 25 ◽  
pp. S428
Author(s):  
Wendy J. Noble ◽  
Michelle A. Utton ◽  
Brian H. Anderton ◽  
Diane P. Hanger
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Fast Axonal Transport

Modeling Bidirectional Transport of New and Used Organelles in Fast Axonal Transport in Neurons

2010 ◽  
Vol 133 (1) ◽  
Author(s):  
A. V. Kuznetsov
Keyword(s):  
Axonal Transport ◽  
Cell Body ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Fast Axonal Transport ◽  
Concentration Difference ◽  
Neuron Body ◽  
Microtubule Polarity ◽  
Bidirectional Transport ◽  
The Right

This paper develops a model for simulating transport of newly synthesized material from the neuron body toward the synapse of the axon as well as transport of misfolded and aggregated proteins back to the neuron body for recycling. The model demonstrates that motor-assisted transport, much similar to diffusion, can occur due to a simple concentration difference between the cell body and the synapse; organelles heading to the synapse do not need to attach preferably to plus-end-directed molecular motors, same as organelles heading to the neuron body for recycling do not need to attach preferably to minus-end-directed molecular motors. The underlying mechanics of molecular-motor-assisted transport is such that organelles would be transported to the right place even if new and used organelles had the same probability of attachment to plus-end-directed (and minus-end-directed) motors. It is also demonstrated that the axon with organelle traps and a region with a reversed microtubule polarity would support much smaller organelle fluxes of both new and used organelles than a healthy axon. The flux of organelles is shown to decrease as the width of organelle traps increases.

A four kinetic state model of fast axonal transport: Model formulation and perturbation solution

Open Physics ◽  
2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrey Kuznetsov
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Transport Model ◽  
Molecular Motor ◽  
Perturbation Solution ◽  
State Model ◽  
Model Formulation ◽  
Fast Axonal Transport ◽  
First Order ◽  
Proposed Model

AbstractThis paper formulates a four kinetic state model for fast axonal transport. The paper further develops the Smith-Simmons model that is based on equations governing intracellular molecular-motor-assisted transport; these equations are extended by considering four rather than three kinetic states for organelles. The model considers plus-end and minus-end-oriented organelles that can be either free (suspended in the cytosol) or attached to microtubules (MTs) (in the latter case organelles are transported by molecular motors). The paper then develops a method for uncoupling differential equations of the proposed model. A perturbation solution of this problem is obtained. The effect of transition between plus-end-oriented and minus-end oriented organelles is discussed. The accuracy of the obtained perturbation solution is evaluated by comparing the zero-order and the first-order results with a high-accuracy numerical solution.

scholarly journals Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

2020 ◽  
Author(s):  
Viktor K. Lund ◽  
Matthew D. Lycas ◽  
Anders Schack ◽  
Rita C. Andersen ◽  
Ulrik Gether ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Long Range ◽  
Molecular Motors ◽  
Critical Role ◽  
Model System ◽  
Small Gtpase ◽  
Dense Core ◽  
Fast Axonal Transport ◽  
Dense Core Vesicles ◽  
Motility Factor

SUMMARYLong range fast axonal transport of neuropeptide-containing dense core vesicles (DCVs), endolysosomal organelles and presynaptic components is critical for maintaining the functionality of neurons. How the transport of DCVs is orchestrated remains an important unresolved question. The small GTPase Rab2 has previously been shown to mediate DCV biogenesis and endosome-lysosome fusion. Here we use the Drosophila model system to demonstrate that Rab2 also plays a critical role in bidirectional axonal transport of DCVs, endosomes and lysosomal organelles, most likely by controlling molecular motors. We further show that the lysosomal motility factor Arl8 is required as well for axonal transport of DCVs, but unlike Rab2 is also critical for DCV exit from cell bodies into axons. Our results uncover the mechanisms responsible for axonal transport of DCVs and reveal surprising parallels between the regulation of DCVs and lysosomal motility.

scholarly journals The Sphingolipid Psychosine Inhibits Fast Axonal Transport in Krabbe Disease by Activation of GSK3  and Deregulation of Molecular Motors

2013 ◽  
Vol 33 (24) ◽  
pp. 10048-10056 ◽  
Author(s):  
L. Cantuti Castelvetri ◽  
M. I. Givogri ◽  
A. Hebert ◽  
B. Smith ◽  
Y. Song ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Krabbe Disease ◽  
Fast Axonal Transport

Simulation of Traffic Jam Formation in Fast Axonal Transport

2009 ◽  
Author(s):  
A. V. Kuznetsov ◽  
A. A. Avramenko ◽  
D. G. Blinov
Keyword(s):  
Alzheimer’S Disease ◽  
Neurodegenerative Diseases ◽  
Axonal Transport ◽  
Tau Protein ◽  
Molecular Motors ◽  
Mechanistic Explanation ◽  
Fast Axonal Transport ◽  
Traffic Jam ◽  
Traffic Jams ◽  
Insight Into

Many neurodegenerative diseases, such as Alzheimer’s disease, are linked to swellings occurring in long arms of neurons. Many scientists believe that these swellings result from traffic jams caused by the failure of intracellular machinery responsible for fast axonal transport; such traffic jam can plug an axon and prevent the sufficient amount of organelles to be delivered toward the synapse of the axon. Mechanistic explanation of the formation of traffic jams in axons induced by overexpression of tau protein is based on the hypothesis that the traffic jam is caused not by the failure of molecular motors to transport organelles along individual microtubules but rather by the disruption of the microtubule system in an axon, by the formation of a swirl of disoriented microtubules at a certain location in the axon. This paper investigates whether a microtubule swirl itself, without introducing into the model microtubule discontinuities in the traffic jam region, is capable of capturing the traffic jam formation. The answer to this question can provide important insight into the mechanics of the formation of traffic jams in axons.

Molecular motors and fast axonal transport

1994 ◽  
Vol 52 ◽  
pp. 22-23
Author(s):  
S. T. Brady
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Fast Axonal Transport ◽  
New Era ◽  
Giant Axons ◽  
New Class ◽  
Atp Analogues ◽  
Intracellular Motility

When video microscopy was first used to study fast axonal transport in isolated axoplasm from squid giant axons, a torrent of membrane traffic was seen to move in both directions. Images of membrane bounded organelles (MBOs) moving along individual microtubules (MTs) in axoplasm opened the way for characterization of the microscopic properties of fast axonal transport and led to the characterization of two molecular motors involved in fast axonal transport. The pharmacology of MBO movement ruled out previously identified molecular motors and a biochemical dissection of fast axonal transport in axoplasm demonstrated the existence of a new class of molecular motors. Subsequently, the polypeptides comprising a new class of molecular motor, kinesin, were discovered initiating a new era in the study of molecular motors and intracellular motility.The effects of ATP analogues on fast axonal transport led to dicovery of kinesin. When the nonhydrolyzable ATP analogue, adenylyl 5′-imidodiphosphate (AMP-PNP), was perfused into isolated axoplasm, all MBOs moving in both anterograde and retrograde directions stopped moving and remained attached to MTs. Unlike the effects of AMP-PNP on myosin and dynein, inhibition by AMP-PNP was rapid even in the presence of equimolar ATP, but was reversed by excess ATP.

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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