Cited by 74Neuroscience and Neuropharmacology ResearchMicrotubule and mitosis dynamicsCellular transport and secretion

Transport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity

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McVicker, Derrick P., Awe, Adam M., Richters, Karl E., Wilson, Rebecca L., Cowdrey, Diana A., Hu, Xindao, Chapman, Edwin R., Dent, Erik W.·2016·Nature Communications

Abstract

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.”

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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)
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
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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