Transport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity
Open accessAbstract
Synaptic plasticity often involves changes in the structure and composition of dendritic spines. Vesicular cargos and organelles enter spines either by exocytosing in the dendrite shaft and diffusing into spines or through a kinesin to myosin hand-off at the base of spines. Here we present evidence for microtubule (MT)-based targeting of a specific motor/cargo pair directly into hippocampal dendritic spines. During transient MT polymerization into spines, the kinesin KIF1A and an associated cargo, synaptotagmin-IV (syt-IV), are trafficked in unison along MTs into spines. This trafficking into selected spines is activity-dependent and results in exocytosis of syt-IV-containing vesicles in the spine head. Surprisingly, knockdown of KIF1A causes frequent fusion of syt-IV-containing vesicles throughout the dendritic shaft and diffusion into spines. Taken together, these findings suggest a mechanism for targeting dendritic cargo directly into spines during synaptic plasticity and indicate that MT-bound kinesins prevent unregulated fusion by sequestering vesicular cargo to MTs.
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Some microtubule-related genes associated with axonal transport and known to play a role in post-mitotic neural wiring and plasticity are associated with signals of positive selection, such as KIF18A or KATNA1.
“Some of the aforementioned microtubule-related genes, specifically those associated with axonal transport and known to play a role in post-mitotic neural wiring and plasticity93, are associated with signals of positive selection, such as KIF18A94 or KATNA195,96.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [94]
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- Authors
- McVicker, D. P., Awe, A. M., Richters, K. E., Wilson, R. L., Cowdrey, D. A., Hu, X., Chapman, E. R., & Dent, E. W.
- Affiliations
- University of Wisconsin–Madison (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Dent, Erik W.
- Venue
- Nature Communications
- Published
- 2016-09-23
- Volume
- 7
- Issue
- 1
- Pages
- 12741-12741
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5411814
- OpenAlex
- W2522204110
- Cited by
- 74
- References
- 42
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 13 · 2020: 5 · 2019: 12 · 2018: 6 · 2017: 4 · 2016: 1
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- Georgia Clinical and Translational Science Alliance (UL1TR000427)
- National Institutes of Health (UL1TR000427)
- National Institute of Mental Health (R01MH061876)
- National Institute of Neurological Disorders and Stroke (R01NS098372, R01NS064014, R01NS080928, F32NS089199)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- dendritic spines, synaptic plasticity, synaptotagmin IV, microtubules, vesicle exocytosis, vesicle fusion, hippocampus, dendritic transport
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