Huntingtin differentially regulates the axonal transport of a sub-set of Rab-containing vesicles in vivo
Open accessAbstract
Loss of huntingtin (HTT), the Huntington's disease (HD) protein, was previously shown to cause axonal transport defects. Within axons, HTT can associate with kinesin-1 and dynein motors either directly or via accessory proteins for bi-directional movement. However, the composition of the vesicle-motor complex that contains HTT during axonal transport is unknown. Here we analyze the in vivo movement of 16 Rab GTPases within Drosophila larval axons and show that HTT differentially influences the movement of a particular sub-set of these Rab-containing vesicles. While reduction of HTT perturbed the bi-directional motility of Rab3 and Rab19-containing vesicles, only the retrograde motility of Rab7-containing vesicles was disrupted with reduction of HTT. Interestingly, reduction of HTT stimulated the anterograde motility of Rab2-containing vesicles. Simultaneous dual-view imaging revealed that HTT and Rab2, 7 or 19 move together during axonal transport. Collectively, our findings indicate that HTT likely influences the motility of different Rab-containing vesicles and Rab-mediated functions. These findings have important implications for our understanding of the complex role HTT plays within neurons normally, which when disrupted may lead to neuronal death and disease.
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The normal huntingtin protein is multifunctional, with roles in transcriptional regulation, vesicular transport, and synaptic transmission.
“The normal huntingtin protein is multifunctional, with roles in transcriptional regulation, vesicular transport, and synaptic transmission [164,165,166].”
From The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases (2025) · cites this paper as [164]
The section “Huntingtin regulates the axonal movement of a particular sub-set of Rab-containing vesicles” (page not provided) supports a role for normal huntingtin in vesicular transport. The paper also discusses huntingtin’s roles at synapses, but does not establish a role in synaptic transmission specifically; no passage found supports transcriptional regulation. (LLM, conf=0.86)
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Vitet, H., Bruyère, J., Xu, H., Séris, C., Brocard, J., Abada, Y.-S., Delatour, B., Scaramuzzino, C., Venance, L., & Saudou, F. (2023) · eLife · doi:10.7554/elife.81011 · Cited by 13 · see citing works
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“The normal huntingtin protein is multifunctional, with roles in transcriptional regulation, vesicular transport, and synaptic transmission [164–166].”
- Authors
- White, J. A., Anderson, E., Zimmerman, K., Zheng, K. H., Rouhani, R., & Gunawardena, S.
- Affiliations
- University at Buffalo, State University of New York (US)
- Corresponding author
- Gunawardena, Shermali
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-10-08
- Volume
- 24
- Issue
- 25
- Pages
- 7182-7195
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC4664163
- OpenAlex
- W2216685026
- Cited by
- 67
- References
- 75
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 13 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 10 · 2016: 2
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH/NINDS (R03-NS084386-01)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- huntingtin, axonal transport, Rab GTPases, Rab2, Rab7, retrograde transport, anterograde transport, kinesin-1, dynein, Huntington's disease
- MeSH terms
- rab7 GTP-Binding Proteins, Animals, Axonal Transport, Drosophila, Nerve Tissue Proteins, Neurons, rab GTP-Binding Proteins, rab2 GTP-Binding Protein
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