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  • Kuznetsov, Ivan A.  (2)
  • Linguistics  (2)
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  • Linguistics  (2)
  • 1
    Online Resource
    Online Resource
    How old are dense-core vesicles residing in en passant boutons: simulation of the mean age of dense-core vesicles in axonal arbours accounting for resident and transiting vesicle populations
    The Royal Society ; 2020
    In:  Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences Vol. 476, No. 2241 ( 2020-09)
    Details
    In: Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, The Royal Society, Vol. 476, No. 2241 ( 2020-09)
    Abstract: In neurons, neuropeptides are synthesized in the soma and are then transported along the axon in dense-core vesicles (DCVs). DCVs are captured in varicosities located along the axon terminal called en passant boutons, which are active terminal sites that accumulate and release neurotransmitters. Recently developed experimental techniques allow for the estimation of the age of DCVs in various locations in the axon terminal. Accurate simulation of the mean age of DCVs in boutons requires the development of a model that would account for resident, transiting-anterograde and transiting-retrograde DCV populations. In this paper, such a model is developed. The model is applied to simulating DCV transport in Drosophila type II motoneurons. The model simulates DCV transport and capture in the axon terminals and makes it possible to predict the age density distribution of DCVs in en passant boutons as well as DCV mean age in boutons. The predicted prevalence of older organelles in distal boutons may explain the ‘dying back’ pattern of axonal degeneration observed in dopaminergic neurons in Parkinson's disease. The predicted difference of two hours between the age of older DCVs residing in distal boutons and the age of younger DCVs residing in proximal boutons is consistent with an approximate estimate of age difference deduced from experimental observations. The age density of resident DCVs is found to be bimodal, which is because DCVs are captured from two transiting states: the anterograde transiting state that contains younger DCVs and the retrograde transiting state that contains older DCVs.
    Type of Medium: Online Resource
    ISSN: 1364-5021 , 1471-2946
    URL: Article
    DOI: 10.1098/rspa.2020.0454
    Language: English
    Publisher: The Royal Society
    Publication Date: 2020
    detail.hit.zdb_id: 209241-4
    detail.hit.zdb_id: 1460987-3
    SSG: 11
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Computational investigation of the effect of reduced dynein velocity and reduced cargo diffusivity on slow axonal transport
    The Royal Society ; 2023
    In:  Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences Vol. 479, No. 2271 ( 2023-03)
    Details
    In: Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, The Royal Society, Vol. 479, No. 2271 ( 2023-03)
    Abstract: Contributions of three components of slow axonal transport (SAT) were studied using a computational model: the anterograde motor (kinesin)-driven component, the retrograde motor (dynein)-driven component and the diffusion-driven component. The contribution of these three components of SAT was investigated in three different segments of the axon: the proximal portion, the central portion, and the distal portion of the axon. MAP1B protein was used as a model system to study SAT because there are published experimental data reporting MAP1B distribution along the axon length and average velocity of MAP1B transport in the axon. This allows the optimization approach to be used to find values of model kinetic constants that give the best fit with published experimental data. The effects of decreasing the value of cargo diffusivity on the diffusion-driven component of SAT and decreasing the value of dynein velocity on the retrograde motor-driven component of SAT were investigated. We found that for the case when protein diffusivity and dynein velocity are very small, it is possible to obtain an analytical solution to model equations. We found that, in this case, the protein concentration in the axon is uniform. This shows that anterograde motor-driven transport alone cannot simulate a variation of cargo concentration in the axon. Most proteins are non-uniformly distributed in axons. They may exhibit, for example, an increased concentration closer to the synapse. The need to reproduce a non-uniform distribution of protein concentration may explain why SAT is bidirectional (in addition to an anterograde component, it also contains a retrograde component).
    Type of Medium: Online Resource
    ISSN: 1364-5021 , 1471-2946
    URL: Article
    DOI: 10.1098/rspa.2022.0672
    Language: English
    Publisher: The Royal Society
    Publication Date: 2023
    detail.hit.zdb_id: 209241-4
    detail.hit.zdb_id: 1460987-3
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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