Molecular mechanisms governing axonal transport: a <i>C. elegans</i> perspective

Vasudevan, Amruta; Koushika, Sandhya P.

doi:10.1080/01677063.2020.1823385

Cited by 8 publications

(3 citation statements)

References 187 publications

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“…Similar to vertebrates, in C. elegans , kinesin-3 (Unc104) is thought to act as major kinesin transporting PVs with an SV protein cargo [ 5 , 82 , 118 , 125 ]. Upon Unc104 depletion, few SVs are observed at the synapse, and synapse number and size are reduced, while SVs accumulate in the cell body [ 100 ].…”

Section: Kinesins and Their Presynaptic Precursor Vesicle Cargosmentioning

confidence: 99%

Presynaptic Precursor Vesicles—Cargo, Biogenesis, and Kinesin-Based Transport across Species

Petzoldt

2023

Cells

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The faithful formation and, consequently, function of a synapse requires continuous and tightly controlled delivery of synaptic material. At the presynapse, a variety of proteins with unequal molecular properties are indispensable to compose and control the molecular machinery concerting neurotransmitter release through synaptic vesicle fusion with the presynaptic membrane. As presynaptic proteins are produced mainly in the neuronal soma, they are obliged to traffic along microtubules through the axon to reach the consuming presynapse. This anterograde transport is performed by highly specialised and diverse presynaptic precursor vesicles, membranous organelles able to transport as different proteins such as synaptic vesicle membrane and membrane-associated proteins, cytosolic active zone proteins, ion-channels, and presynaptic membrane proteins, coordinating synaptic vesicle exo- and endocytosis. This review aims to summarise and categorise the diverse and numerous findings describing presynaptic precursor cargo, mode of trafficking, kinesin-based axonal transport and the molecular mechanisms of presynaptic precursor vesicles biogenesis in both vertebrate and invertebrate model systems.

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Section: Kinesins and Their Presynaptic Precursor Vesicle Cargosmentioning

confidence: 99%

Presynaptic Precursor Vesicles—Cargo, Biogenesis, and Kinesin-Based Transport across Species

Petzoldt

2023

Cells

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“…Motion properties of moving vesicles, such as run length, velocity, and pause duration fraction can be influenced by the number of microtubule-dependent motors on the vesicle surface, posttranslational modifications (PTMs) and microtubule-associated proteins (MAPs) on the underlying microtubule tracks, and presence of crowded environments (Sabharwal andKoushika, 2019, Vasudevan andKoushika, 2020). We find that anterogradely-moving pre-SVs turning into the branch have higher segment run lengths and velocities than pre-SVs that pause at the branch point (Figs.…”

Section: Synaptic Vesicles Entering the Branch Have Distinct Motion P...mentioning

confidence: 99%

Preferential transport of synaptic vesicles across neuronal branches is regulated by the levels of the anterograde motor UNC-104/KIF1A

Vasudevan

Ratnakaran

Murthy

et al. 2023

Preprint

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Asymmetric transport of cargo across axonal branches is a field of active research. Mechanisms contributing to preferential cargo transport along specific branchesin vivoin wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the synaptic branch or pause at the branch point inC. elegansPLM neurons. The anterograde motor UNC-104/KIF1A regulates this vesicle behaviour at the branch point. Reduced levels of functional UNC-104 cause vesicles to predominantly pause at the branch point and lose their preference for turning into the synaptic branch. SAM-4/Myrlysin, which aids in recruitment/activation of UNC-104 on synaptic vesicles, regulates vesicle behaviour at the branch point similar to UNC-104. Increasing the levels of UNC-104 increases the preference of vesicles to go straight towards the asynaptic end. This suggests that the neuron optimises UNC-104 levels on the cargo surface to maximise the fraction of vesicles entering the branch and minimise the fraction going to the asynaptic end.

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“…Axonal transport functions to deliver and distribute cellular growth factors, organelles, synaptic cargoes and cytoskeletal factors to increase the efficiency of trafficking within neuronal cells [ 139 ]. Impaired axonal transport is observed in mouse models and post-mortem tissues of patients with ALS [ 140 ].…”

Section: Pathogenic Mechanisms Of Tdp-43 In Cell and Animal Modelsmentioning

confidence: 99%

Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

Wood

Gurfinkel

Polain

et al. 2021

IJMS

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Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. The pathogenicity of TDP-43 cytoplasmic aggregates may be linked with both a loss of nuclear function and a gain of toxic functions. The cellular processes involved in ALS and FTLD disease pathogenesis include changes to RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments to axonal transport and autophagy, abnormal neuromuscular junctions, endoplasmic reticulum stress and the subsequent induction of the unfolded protein response. Here, we review and discuss the evidence for alterations to these processes that have been reported in cellular and animal models of TDP-43 proteinopathy.

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Molecular mechanisms governing axonal transport: a C. elegans perspective

Cited by 8 publications

References 187 publications

Presynaptic Precursor Vesicles—Cargo, Biogenesis, and Kinesin-Based Transport across Species

Presynaptic Precursor Vesicles—Cargo, Biogenesis, and Kinesin-Based Transport across Species

Preferential transport of synaptic vesicles across neuronal branches is regulated by the levels of the anterograde motor UNC-104/KIF1A

Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

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