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Differentiation between oppositely oriented microtubules controls polarized neuronal transport

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Tas, Roderick P., Chazeau, Anaël, Cloin, Bas M.C., Lambers, Maaike L.A., Hoogenraad, Casper C., Kapitein, Lukas C.·2017·Neuron
DOI 10.1016/j.neuron.2017.11.018PMC PMC5746200
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Abstract

Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely. In addition, microtubules with similar orientations and modifications form bundles that bias transport. Importantly, because the plus-end-directed Kinesin-1 selectively interacts with acetylated microtubules, this organization guides this motor out of dendrites and into axons. In contrast, Kinesin-3 prefers tyrosinated microtubules and can enter both axons and dendrites. This separation of distinct microtubule subsets into oppositely oriented bundles constitutes a key architectural principle of the neuronal microtubule cytoskeleton that enables polarized sorting by different motor proteins.

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  • Acetylated MTs are oriented uniformly with their minus ends toward the distal end in dendrites.

    “recent studies suggest that acetylated MTs are oriented uniformly with their minus ends toward the distal end in dendrites (15).”

    From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [15]

    The Results section, “Minus-End-Out-Oriented Microtubules Are More Stable and More Acetylated” (page not provided), reports that acetylated dendritic microtubules predominantly overlap with minus-end-out microtubules. That supports a preferred orientation toward the distal end, but not the claim that their orientation is uniform. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Tas et al. also showed that acetylated and tyrosinated MTs are separated, and that acetylated MT fraction contains more minus-end-out MTs than tyrosinated MTs (66% vs 34%).

    “They also showed that acetylated and tyrosinated MTs are separated, and that acetylated MT fraction contains more minus-end-out MTs than tyrosinated MTs (66% vs 34%).”

    From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [15]

    The Results section reports that acetylated and tyrosinated microtubules form spatially separated subsets, and that acetylated microtubules predominantly overlap with minus-end-out microtubules. But the 66% versus 34% figures describe microtubule orientations in a stable network remaining after nocodazole treatment, not a comparison of the acetylated and tyrosinated fractions. The passage also inconsistently assigns those figures to plus- and minus-end-out microtubules, respectively, despite saying minus-end-out microtubules were more abundant. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The G234A rigor mutant of Kinesin-1 binds to and effectively decorates acetylated microtubules.

    “Similar to the active motor, the G234A rigor mutant of Kinesin-1 binds to and effectively decorates acetylated MTs (Tas et al., 2017; Guardia et al., 2016; Farías et al., 2017).”

    From A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle (2023) · cites this paper as Tas et al., 2017

    The Results section (page unavailable) reports that a Kif5a rigor mutant binds microtubules and shows dramatic colocalization with acetylated tubulin, supporting the binding and decoration claim. Our copy does not identify that mutant as G234A, so it does not verify the specific mutation attributed to this source. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Two models have been proposed to explain microtubule stability in axons: one suggests centrally located microtubules are generally more stable while peripheral ones are more dynamic, and the other suggests intra-microtubule heterogeneity with alternating domains of differing stability.

    “Two models have been proposed to explain microtubule stability in axons: one suggests that centrally located microtubules are generally more stable while peripheral ones are more dynamic53–55, and the other model suggests intra-microtubule heterogeneity, in which individual microtubules contain alternating domains with differing stability56,57.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [55]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Tas et al. reported that plus-end-out and minus-end-out MTs are bundled and separated in dendrites, promoting persistent moving in a certain direction because of reduced potential switching to oppositely oriented MTs.

    “Tas et al. reported that plus-end-out and minus-end-out MTs are bundled and separated in dendrites, promoting persistent moving in a certain direction because of reduced potential switching to oppositely oriented MTs (15).”

    From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [15]

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Authors
Tas, R. P., Chazeau, A., Cloin, B. M. C., Lambers, M. L. A., Hoogenraad, C. C., & Kapitein, L. C.
Affiliations
Utrecht University (NL)
Corresponding author
Kapitein, Lukas C.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2017-12
Volume
96
Issue
6
Pages
1264-1271.e5
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2017.11.018
PMC
PMC5746200
OpenAlex
W2771928043
Cited by
306
References
1
Citations by year
2026: 23 · 2025: 39 · 2024: 34 · 2023: 28 · 2022: 36 · 2021: 39 · 2020: 54 · 2019: 32 · 2018: 21
FWCI
3.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • Netherlands Organization for Scientific Research (NWO) (NWO-ALW-VICI, NWO-ALW-VIDI)
  • Dutch Technology Foundation STW (NWO-NANO)
  • European Research Council (ERC Starting Grant, ERC Consolidator Grant, Marie Curie fellowship)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
microtubule polarity, microtubule acetylation, microtubule stability, microtubule bundles, kinesin-1, kinesin-3, dendrites, axons, microtubule cytoskeleton, super-resolution microscopy
MeSH terms
Animals, Axons, Cell Differentiation, Dendrites, Microtubule-Associated Proteins, Microtubules, Models, Neurological, Neurons, Kinesins, Cell Polarity, Protein Transport

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