ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2024
Rab6-Mediated Polarized Transport of Synaptic Vesicle Precursors Is Essential for the Establishment of Neuronal Polarity and Brain Formation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- CAST controls presynaptic sequestration of Rab6 in neurons.Molecular brain · 2026Article
- Persistent PirB cleavage drives Golgi-directed trafficking deficits underlying neurodegeneration.Translational neurodegeneration · 2026Article
- Astrocyte heterogeneity and hierarchical information flow: reframing glial computation.Frontiers in cellular neuroscience · 2026Article
- A mutation inMolecular vision · 2026Article
- Molecular mechanisms of polarized transport to the apical plasma membrane.Frontiers in cell and developmental biology · 2024Review
- The neuronal Golgi in neural circuit formation and reorganization.Frontiers in neural circuits · 2024Review
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Authors and funding
5 authors.
Funding
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Abstract
Neurons are highly polarized cells that are composed of a single axon and multiple dendrites. Axon-dendrite polarity is essential for proper tissue formation and brain functions. Intracellular protein transport plays an important role in the establishment of neuronal polarity. However, the regulatory mechanism of polarized transport remains unclear. Here, we show that Rab6, a small GTPase that acts on the regulation of intracellular vesicular trafficking, plays key roles in neuronal polarization and brain development. Central nervous system-specific Rab6a/b double knock-out (Rab6 DKO) mice of both sexes exhibit severe dysplasia of the neocortex and the cerebellum. In the Rab6 DKO neocortex, impaired axonal extension of neurons results in hypoplasia of the intermediate zone. In vitro, deletion of Rab6a and Rab6b in cultured neurons from both sexes causes the abnormal accumulation of synaptic vesicle precursors (SVPs) adjacent to the Golgi apparatus, which leads to defects in axonal extension and the loss of axon-dendrite polarity. Moreover, Rab6 DKO causes significant expansion of lysosomes in the soma in neurons. Overall, our results reveal that Rab6-mediated polarized transport of SVPs is crucial for neuronal polarization and subsequent brain formation.
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