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.

Modeling the Effect of Vesicle Traps on Mass Transfer and Traffic Jam Formation in Fast Axonal Transport

2010 ◽  
Author(s):  
Andrey V. Kuznetsov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mass Transfer ◽  
Neurodegenerative Diseases ◽  
Axonal Transport ◽  
Structural Changes ◽  
Molecular Motor ◽  
Fast Axonal Transport ◽  
Traffic Jam ◽  
The Right

This paper simulates effects of structural changes in the microtubule (MT) system on mass transfer in an axon. Understanding this process is important for understanding the underlying reasons for many neurodegenerative diseases, such as Alzheimer’s disease. In particular, it is investigated how the degree of polar mismatching in an MT swirl affects organelle trap regions in the axon and inhibiting transport of organelles down the axon. The model is based on modified Smith-Simmons equations governing molecular-motor-assisted transport in neurons. It is established that the structure that develops as a result of a region with disoriented MTs (the MT swirl) consists of two organelle traps, the trap to the left of the swirl region accumulates plus-end oriented organelles and the trap to the right of this region accumulates minus-end oriented organelles. The presence of such a structure is shown to decrease the transport of organelles toward the synapse of the axon. Four cases with a different degree of polar mismatching in the swirl region are investigated; the results are compared with simulations for a healthy axon, in which case organelle traps are absent.

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.

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

scholarly journals Bidirectional transport of fluorescently labeled vesicles introduced into extruded axoplasm of squid Loligo pealei.

1984 ◽  
Vol 99 (2) ◽  
pp. 445-452 ◽  
Author(s):  
S P Gilbert ◽  
R D Sloboda
Keyword(s):  
Axonal Transport ◽  
Giant Axon ◽  
Epifluorescence Microscopy ◽  
Differential Interference Contrast Microscopy ◽  
Fast Axonal Transport ◽  
Bidirectional Transport ◽  
Interference Contrast Microscopy ◽  
The Mean ◽  
Loligo Pealei ◽  
Vesicle Movement

A reconstituted model was devised to study the mechanisms of fast axonal transport in the squid Loligo pealei. Axonal vesicles were isolated from axoplasm of the giant axon and labeled with rhodamine-conjugated octadecanol, a membrane-specific fluorescent probe. The labeled vesicles were then injected into a fresh preparation of extruded axoplasm in which endogenous vesicle transport was occurring normally. The movement of the fluorescent, exogenous vesicles was observed by epifluorescence microscopy for as long as 5 min without significant photobleaching, and the transport of endogenous, nonfluorescent vesicles was monitored by video-enhanced differential interference-contrast microscopy. The transport of fluorescent, exogenous vesicles was shown to be bidirectional and ATP-dependent and occurred at a mean rate of 6.98 +/- 4.11 micron/s (mean +/- standard deviation, n = 41). In comparison, the mean rate of transport of nonfluorescent, endogenous vesicles in control axoplasm treated with vesicle buffer alone was 4.76 +/- 1.60 micron/s (n = 64). These rates are slightly higher than the mean rate of endogenous vesicle movement in extruded axoplasm (3.56 +/- 1.05 micron/s, n = 40) not subject to vesicles or vesicle buffer. Not all vesicles and organelles, exogenous or endogenous, were observed to move. In experiments in which proteins of the surface of the fluorescent vesicles were digested with trypsin before injection, no movement of the fluorescent vesicles was observed, although the transport of endogenous vesicles and organelles appeared to proceed normally. The results summarized above indicate that isolated vesicles, incorporated into axoplasm, move with the characteristics of fast axonal transport. Because the vesicles are fluorescent, they can be readily distinguished from nonfluorescent, endogenous vesicles. Moreover, this system permits vesicle characteristics to be experimentally manipulated, and therefore may prove valuable for the elucidation of the mechanisms of fast axonal transport.

scholarly journals AXONAL TRANSPORT OF NEWLY SYNTHESIZED GLYCOPROTEINS IN A SINGLE IDENTIFIED NEURON OF APLYSIA CALIFORNICA

1974 ◽  
Vol 61 (3) ◽  
pp. 665-675 ◽  
Author(s):  
Richard T. Ambron ◽  
James E. Goldman ◽  
James H. Schwartz
Keyword(s):  
Axonal Transport ◽  
Cell Body ◽  
Aplysia Californica ◽  
Identified Neuron ◽  
The Right ◽  
Aplysia Neuron

Increasing amounts of glycoprotein synthesized from L-[3H]fucose injected into the cell body of R2, an identified Aplysia neuron, were found in the right pleuro-abdominal connective. Autoradiography revealed that the glycoproteins were localized in the axon of R2. Glycoproteins appearing in the axon presumably were synthesized in the cell body, since no significant incorporation was observed when [3H]fucose was injected directly into the axon. [3H]glycoproteins were detected in the connective after a delay of 1 h after intrasomatic injection. Thereafter, transport from the cell body was rapid, and by 10 h after injection, 45% of the total neuronal [3H]glycoprotein had appeared in the axon. By analysing the radioactivity in cell body and connective 4, 10, and 15 h after injection, we found that [3H]glycoproteins were transported selectively compared to nonmacromolecular material. Sequential sectioning of the connective revealed that [3H]glycoproteins were transported in discrete waves. The population of membrane-associated [3H]glycoproteins in the axon differed from that in the cell body. Two of the five somatic components appeared to be transported preferentially. In addition a new component appeared in the axon 10 h after injection.

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.

scholarly journals Looking at Slow Axonal Transport

1996 ◽  
Vol 4 (9) ◽  
pp. 3-5
Author(s):  
Stephen W. Carmichael ◽  
W. Stephen Brimijoin
Keyword(s):  
Protein Synthesis ◽  
Axonal Transport ◽  
Nerve Cell ◽  
Cell Body ◽  
Nerve Cell Body ◽  
Slow Axonal Transport ◽  
Fast Axonal Transport ◽  
Neuronal Proteins ◽  
Axonal Process ◽  
Proteins And Peptides

Neurons are about as polarized as cells ever get. Their axonal process can extend a distance that is up to a million times the diameter of the nerve cell body. Axons have none of the ribosomal machinery responsible for protein synthesis, so all neuronal proteins and peptides must be manufactured near the nucleus and carried out to the periphery. This distribution involves at least two distinct mechanisms, fast axonal transport, moving at almost 500 mm per day, and slow axonal transport, moving only 0.1 to 3 mm per day. It turns out that proteins of the neuronal cytoskeleton, along with many soluble cytosolic proteins, are transported exclusively by the slower process.

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