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<p>Transport of dense core vesicles (DCVs) in neurons is crucial for distributing molecules like neuropeptides and growth factors. We studied the experimental trajectories of dynein-driven directed movement of DCVs in the ALA neuron in&#xa0;<i>C. elegans</i> over a duration of up to 6 seconds. We analysed the DCV movement in three strains of <i>C. elegans</i>: (1) with normal kinesin-1 function, (2) with reduced function in kinesin light chain 2 (KLC-2), and (3) a null mutation in kinesin light chain 1 (KLC-1). We find that DCVs move superdiffusively with displacement variance <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41598_2024_83602_Article_IEq1.gif" Format="GIF" Height="20" Rendition="HTML" Resolution="72" Type="Linedraw" Width="84" /> </InlineMediaObject> <EquationSource Format="TEX">\(var(x) \sim t^2\)</EquationSource> </InlineEquation> in all three strains with low reversal rates and frequent immobilization of DCVs. The distribution of DCV displacements fits a beta-binomial distribution with the mean and the variance following linear and quadratic growth patterns, respectively. We propose a simple heterogeneous random walk model to explain the observed superdiffusive retrograde transport behaviour of DCV movement. This model involves a random probability with the beta density for a DCV to resume its movement or remain in the same position. To validate our model further, we measure the first passage time for a DCV to reach a certain threshold for the first time. According to the model, the first passage time distribution should follow a beta-negative binomial distribution with the same parameters as the DCV displacement distributions. Our experimental data confirm this prediction.</p>

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Heterogeneous model for superdiffusive movement of dense core vesicles in C. elegans

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月27日

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  • Anna Gavrilova,
  • Nickolay Korabel,
  • Victoria J. Allan,
  • Sergei Fedotov

摘要

Transport of dense core vesicles (DCVs) in neurons is crucial for distributing molecules like neuropeptides and growth factors. We studied the experimental trajectories of dynein-driven directed movement of DCVs in the ALA neuron in C. elegans over a duration of up to 6 seconds. We analysed the DCV movement in three strains of C. elegans: (1) with normal kinesin-1 function, (2) with reduced function in kinesin light chain 2 (KLC-2), and (3) a null mutation in kinesin light chain 1 (KLC-1). We find that DCVs move superdiffusively with displacement variance \(var(x) \sim t^2\) in all three strains with low reversal rates and frequent immobilization of DCVs. The distribution of DCV displacements fits a beta-binomial distribution with the mean and the variance following linear and quadratic growth patterns, respectively. We propose a simple heterogeneous random walk model to explain the observed superdiffusive retrograde transport behaviour of DCV movement. This model involves a random probability with the beta density for a DCV to resume its movement or remain in the same position. To validate our model further, we measure the first passage time for a DCV to reach a certain threshold for the first time. According to the model, the first passage time distribution should follow a beta-negative binomial distribution with the same parameters as the DCV displacement distributions. Our experimental data confirm this prediction.