ArticleMolecular biology of the cell2015
Mycalolide B dissociates dynactin and abolishes retrograde axonal transport of dense-core vesicles.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Differential axonal trafficking of Neuropeptide Y-, LAMP1-, and RAB7-tagged organelles in vivo.eLife · 2022Article
- Cytoskeletal regulation guides neuronal trafficking to effectively supply the synapse.Current biology : CB · 2021Review
- SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury.Frontiers in cellular neuroscience · 2020Article
- Effect of mycalolides isolated from a marine sponge Mycale aff. nullarosette on actin in living cells.Scientific reports · 2019Article
- Effects of Modulating Actin Dynamics on HER2 Cancer Cell Motility and Metastasis.Scientific reports · 2018Article
- Sentryn and SAD Kinase Link the Guided Transport and Capture of Dense Core Vesicles inGenetics · 2018Article
- Ethanol stimulates the in vivo axonal movement of neuropeptide dense-core vesicles in Drosophila motor neurons.Journal of neurochemistry · 2018Article
- Costorage of High Molecular Weight Neurotransmitters in Large Dense Core Vesicles of Mammalian Neurons.Frontiers in cellular neuroscience · 2018Article
- Review
- Loss of Huntingtin stimulates capture of retrograde dense-core vesicles to increase synaptic neuropeptide stores.European journal of cell biology · 2017Article
- Activity Induces Fmr1-Sensitive Synaptic Capture of Anterograde Circulating Neuropeptide Vesicles.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Dual-Color Herpesvirus Capsids Discriminate Inoculum from Progeny and Reveal Axonal Transport Dynamics.Journal of virology · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Axonal transport is critical for maintaining synaptic transmission. Of interest, anterograde and retrograde axonal transport appear to be interdependent, as perturbing one directional motor often impairs movement in the opposite direction. Here live imaging of Drosophila and hippocampal neuron dense-core vesicles (DCVs) containing a neuropeptide or brain-derived neurotrophic factor shows that the F-actin depolymerizing macrolide toxin mycalolide B (MB) rapidly and selectively abolishes retrograde, but not anterograde, transport in the axon and the nerve terminal. Latrunculin A does not mimic MB, demonstrating that F-actin depolymerization is not responsible for unidirectional transport inhibition. Given that dynactin initiates retrograde transport and that amino acid sequences implicated in macrolide toxin binding are found in the dynactin component actin-related protein 1, we examined dynactin integrity. Remarkably, cell extract and purified protein experiments show that MB induces disassembly of the dynactin complex. Thus imaging selective retrograde transport inhibition led to the discovery of a small-molecule dynactin disruptor. The rapid unidirectional inhibition by MB suggests that dynactin is absolutely required for retrograde DCV transport but does not directly facilitate ongoing anterograde DCV transport in the axon or nerve terminal. More generally, MB's effects bolster the conclusion that anterograde and retrograde axonal transport are not necessarily interdependent.
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