Dynein efficiently navigates the dendritic cytoskeleton to drive the retrograde trafficking of BDNF/TrkB signaling endosomes
Open accessAbstract
The efficient transport of cargoes within axons and dendrites is critical for neuronal function. Although we have a basic understanding of axonal transport, much less is known about transport in dendrites. We used an optogenetic approach to recruit motor proteins to cargo in real time within axons or dendrites in hippocampal neurons. Kinesin-1, a robust axonal motor, moves cargo less efficiently in dendrites. In contrast, cytoplasmic dynein efficiently navigates both axons and dendrites; in both compartments, dynamic microtubule plus ends enhance dynein-dependent transport. To test the predictions of the optogenetic assay, we examined the contribution of dynein to the motility of an endogenous dendritic cargo and found that dynein inhibition eliminates the retrograde bias of BDNF/TrkB trafficking. However, inhibition of microtubule dynamics has no effect on BDNF/TrkB motility, suggesting that dendritic kinesin motors may cooperate with dynein to drive the transport of signaling endosomes into the soma. Collectively our data highlight compartment-specific differences in kinesin activity that likely reflect specialized tuning for localized cytoskeletal determinants, whereas dynein activity is less compartment specific but is more responsive to changes in microtubule dynamics.
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Dynein is reported to transport cargoes both anterogradely and retrogradely in dendrites where orientation of MTs is considered to be mixed.
“Dynein, which moves toward minus-end of MTs, is reported to transport cargoes both anterogradely (38, 39) and retrogradely (40, 41) in dendrites where orientation of MTs is considered to be mixed.”
From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [40]
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A combinatorial MAP code dictates polarized microtubule transport
Monroy, B. Y., Tan, T. C., Oclaman, J. M., Han, J. S., Simó, S., Niwa, S., Nowakowski, D. W., McKenney, R. J., & Ori-McKenney, K. M. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.01.029 · Cited by 157 · see citing works
Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons
Yonemura, Y., Sakai, Y., Nakata, R., Hagita-Tatsumoto, A., Miyasaka, T., & Misonou, H. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113407
- Authors
- Ayloo, S., Guedes-Dias, P., Ghiretti, A. E., & Holzbaur, E. L. F.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Holzbaur, Erika L. F.
- Venue
- Molecular Biology of the Cell
- Published
- 2017-09-15
- Volume
- 28
- Issue
- 19
- Pages
- 2543-2554
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC5597326
- OpenAlex
- W2738059404
- Cited by
- 41
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 4 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 3
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (F32MH108187)
- National Institute of General Medical Sciences (R01GM048661)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cytoplasmic dynein, dendritic transport, retrograde trafficking, BDNF/TrkB signaling, signaling endosomes, kinesin-1, microtubule plus ends, microtubule dynamics, axonal transport, dendritic cytoskeleton, hippocampal neurons, motor protein motility
- MeSH terms
- Animals, Axons, Axonal Transport, Cells, Cultured, Cytoskeleton, Dendrites, Hippocampus, Microtubules, Myosins, Neurons, Endosomes, Signal Transduction, Kinesins, Brain-Derived Neurotrophic Factor, Receptor, trkB, Protein Transport, Rats, Cytoplasmic Dyneins
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