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Microtubule-Based Intracellular Tran...

Gavrilova, Anna,

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Microtubule-Based Intracellular Transport in Neurons and Fibroblasts : Experimental Studies, Data Analysis, and Mathematical Modelling /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Microtubule-Based Intracellular Transport in Neurons and Fibroblasts : Experimental Studies, Data Analysis, and Mathematical Modelling // Anna Gavrilova.
Author:	Gavrilova, Anna,
Description:	1 electronic resource (232 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
Contained By:	Dissertations Abstracts International86-06B.
Subject:	Adenosine. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31760902
ISBN:	9798346788089

Microtubule-Based Intracellular Transport in Neurons and Fibroblasts : Experimental Studies, Data Analysis, and Mathematical Modelling /
Gavrilova, Anna,

Microtubule-Based Intracellular Transport in Neurons and Fibroblasts : Experimental Studies, Data Analysis, and Mathematical Modelling /Anna Gavrilova. - 1 electronic resource (232 pages)

Source: Dissertations Abstracts International, Volume: 86-06, Section: B.

Neuronal transport plays an important role in cellular function, relying on the movement of kinesins and dyneins. While the structural aspects of these motor proteins are well described, their precise mechanisms in organelle movement remain unclear. In this study, we investigated the role of mutations in kinesin light chain 1 (KLC1), kinesin light chain 2 (KLC2), and kinesin heavy chain (KHC) on the transport properties of dense core vesicles (DCVs) in C. elegans. We found surprising results by crossing these mutant strains with the ida-1::gfp strain, which has green fluorescent protein attached to DCVs and imaged their movement. We show that the KLC1 null mutation (klc-1(ok2609)) had no effect on anterograde transport but increased the speed of retrograde transport and extended the lifespan of the worms expressing IDA1::GFP. Additionally, the KLC2 mutation (klc2(km11)) decreased DCV movement in both directions, prolonged worm lifespan, and reduced the frequency of body bends during swimming. Finally, the KHC mutation (unc116(rh24sb79)) significantly impaired transport in both directions, shortened lifespan and greatly diminished swimming ability. Our findings suggest that kinesin-1 not only influences anterograde and retrograde transport but also plays a crucial role in regulating the lifespan and behaviour of the whole animal. We conducted a mathematical analysis of this data and discovered that DCVs exhibit superdiffusive movement with displacement variance var(x) ∼ t2across strains with KLC mutations and worms without mutations, characterized by low reversal rates and frequent immobilization. The distribution of DCV displacements fits a beta-binomial distribution, driving us to propose a heterogeneous random walk model to explain the superdiffusive retrograde transport behaviour.Furthermore, we demonstrate the anomalous nature of endosome transport along microtubules and develop a neural network to segment endosome trajectories into persistent and antipersistent movements. We introduce a novel persistent random walk model with a rest state for the stochastic transport of endosomes and validate its applicability using real biological data.

English

ISBN: 9798346788089Subjects--Topical Terms:

1362513
Adenosine.

Microtubule-Based Intracellular Transport in Neurons and Fibroblasts : Experimental Studies, Data Analysis, and Mathematical Modelling /
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520 $a Neuronal transport plays an important role in cellular function, relying on the movement of kinesins and dyneins. While the structural aspects of these motor proteins are well described, their precise mechanisms in organelle movement remain unclear. In this study, we investigated the role of mutations in kinesin light chain 1 (KLC1), kinesin light chain 2 (KLC2), and kinesin heavy chain (KHC) on the transport properties of dense core vesicles (DCVs) in C. elegans. We found surprising results by crossing these mutant strains with the ida-1::gfp strain, which has green fluorescent protein attached to DCVs and imaged their movement. We show that the KLC1 null mutation (klc-1(ok2609)) had no effect on anterograde transport but increased the speed of retrograde transport and extended the lifespan of the worms expressing IDA1::GFP. Additionally, the KLC2 mutation (klc2(km11)) decreased DCV movement in both directions, prolonged worm lifespan, and reduced the frequency of body bends during swimming. Finally, the KHC mutation (unc116(rh24sb79)) significantly impaired transport in both directions, shortened lifespan and greatly diminished swimming ability. Our findings suggest that kinesin-1 not only influences anterograde and retrograde transport but also plays a crucial role in regulating the lifespan and behaviour of the whole animal. We conducted a mathematical analysis of this data and discovered that DCVs exhibit superdiffusive movement with displacement variance var(x) ∼ t2across strains with KLC mutations and worms without mutations, characterized by low reversal rates and frequent immobilization. The distribution of DCV displacements fits a beta-binomial distribution, driving us to propose a heterogeneous random walk model to explain the superdiffusive retrograde transport behaviour.Furthermore, we demonstrate the anomalous nature of endosome transport along microtubules and develop a neural network to segment endosome trajectories into persistent and antipersistent movements. We introduce a novel persistent random walk model with a rest state for the stochastic transport of endosomes and validate its applicability using real biological data.
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650 4 $a Signal transduction. $3 3546420
650 4 $a Neurons. $3 588699
650 4 $a Partial differential equations. $3 2180177
650 4 $a Neural networks. $3 677449
650 4 $a Microscopy. $3 540544
650 4 $a Binomial distribution. $3 3562291
650 4 $a Worms. $3 3561322
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710 2 $a The University of Manchester (United Kingdom). $e degree granting institution. $3 3759026
720 1 $a Fedotov, Sergei Petrovich $e degree supervisor.
720 1 $a Allan, Viki $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 86-06B.
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792 $a 2024
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