ArticlePLoS genetics2014
Genetic analysis of a novel tubulin mutation that redirects synaptic vesicle targeting and causes neurite degeneration in C. elegans.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Worm orthologues of cytokinesis-associated proteins CIT and ASPM regulate neuronal microtubule dynamics and polarity in C. elegans.PLoS genetics · 2026Article
- Decoding the role of microtubules: a trafficking road for vesicle.Theranostics · 2025Review
- C. elegans touch receptor neurons direct mechanosensory complex organization via repurposing conserved basal lamina proteins.Current biology : CB · 2024Article
- Article
- How neurons maintain their axons long-term: an integrated view of axon biology and pathology.Frontiers in neuroscience · 2023Review
- Mutation of the H12-helix of α-tubulin/MEC-12 disrupts the localization of neuronal mitochondria.microPublication biology · 2022Article
- Epistatic, synthetic, and balancing interactions among tubulin missense mutations affecting neurite growth inMolecular biology of the cell · 2021Article
- Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth inDevelopment (Cambridge, England) · 2020Article
- The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology.Neural development · 2019Review
- Presenilin mutations deregulate mitochondrial CaeLife · 2018Article
- Distinct effects of tubulin isotype mutations on neurite growth inMolecular biology of the cell · 2017Article
- Genetic defects in β-spectrin and tau sensitizeeLife · 2017Article
- Dynamic microtubules drive circuit rewiring in the absence of neurite remodeling.Current biology : CB · 2015Article
- Neurodegeneration and microtubule dynamics: death by a thousand cuts.Frontiers in cellular neuroscience · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Neuronal cargos are differentially targeted to either axons or dendrites, and this polarized cargo targeting critically depends on the interaction between microtubules and molecular motors. From a forward mutagenesis screen, we identified a gain-of-function mutation in the C. elegans α-tubulin gene mec-12 that triggered synaptic vesicle mistargeting, neurite swelling and neurodegeneration in the touch receptor neurons. This missense mutation replaced an absolutely conserved glycine in the H12 helix with glutamic acid, resulting in increased negative charges at the C-terminus of α-tubulin. Synaptic vesicle mistargeting in the mutant neurons was suppressed by reducing dynein function, suggesting that aberrantly high dynein activity mistargeted synaptic vesicles. We demonstrated that dynein showed preference towards binding mutant microtubules over wild-type in microtubule sedimentation assay. By contrast, neurite swelling and neurodegeneration were independent of dynein and could be ameliorated by genetic paralysis of the animal. This suggests that mutant microtubules render the neurons susceptible to recurrent mechanical stress induced by muscle activity, which is consistent with the observation that microtubule network was disorganized under electron microscopy. Our work provides insights into how microtubule-dynein interaction instructs synaptic vesicle targeting and the importance of microtubule in the maintenance of neuronal structures against constant mechanical stress.
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