Microtubule Acetylation Promotes Kinesin-1 Binding and Transport
Open accessAbstract
Long-distance intracellular delivery is driven by kinesin and dynein motor proteins that ferry cargoes along microtubule tracks . Current models postulate that directional trafficking is governed by known biophysical properties of these motors-kinesins generally move to the plus ends of microtubules in the cell periphery, whereas cytoplasmic dynein moves to the minus ends in the cell center. However, these models are insufficient to explain how polarized protein trafficking to subcellular domains is accomplished. We show that the kinesin-1 cargo protein JNK-interacting protein 1 (JIP1) is localized to only a subset of neurites in cultured neuronal cells. The mechanism of polarized trafficking appears to involve the preferential recognition of microtubules containing specific posttranslational modifications (PTMs) by the kinesin-1 motor domain. Using a genetic approach to eliminate specific PTMs, we show that the loss of a single modification, alpha-tubulin acetylation at Lys-40, influences the binding and motility of kinesin-1 in vitro. In addition, pharmacological treatments that increase microtubule acetylation cause a redirection of kinesin-1 transport of JIP1 to nearly all neurite tips in vivo. These results suggest that microtubule PTMs are important markers of distinct microtubule populations and that they act to control motor-protein trafficking.
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Increased AcTub stabilizes microtubules and promotes microtubule-based transport.
“Increased AcTub stabilizes microtubules and promotes microtubule-based transport [41]”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [41]
Cytoplasmic dynein transports cargo toward the minus end of MT and binds preferably to acetylated MTs like kinesins.
“Since cytoplasmic dynein transports cargo toward the minus end of MT and binds preferably to acetylated MTs like kinesins (16, 17)”
From Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons (2026) · cites this paper as [16]
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- Authors
- Reed, N. A., Cai, D., Blasius, T. L., Jih, G. T., Meyhofer, E., Gaertig, J., & Verhey, K. J.
- Affiliations
- University of Michigan (US)
- University of Georgia (US)
- Corresponding author
- Verhey, Kristen J.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 16
- Issue
- 21
- Pages
- 2166-2172
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2046746554
- Cited by
- 919
- References
- 5
- Citations by year
- 2026: 17 · 2025: 42 · 2024: 38 · 2023: 49 · 2022: 36 · 2021: 46 · 2020: 56 · 2019: 46 · 2018: 45 · 2017: 49 · 2016: 53 · 2015: 50 · 2014: 57 · 2013: 58 · 2012: 57
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2486 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (MCB-0235826)
- National Institutes of Health (GM070862)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- microtubule acetylation, kinesin-1, alpha-tubulin acetylation, post-translational modification, JIP1, neuronal transport, intracellular transport
- MeSH terms
- Acetylation, Animals, Bacterial Proteins, Chlorocebus aethiops, Drosophila, Dyneins, HeLa Cells, Humans, Luminescent Proteins, Microtubules, Neurons, Protein Binding, Protein Processing, Post-Translational, Tetrahymena, Tubulin, Neurites, Kinesins, Protein Structure, Tertiary, COS Cells, Protein Transport, Adaptor Proteins, Signal Transducing, Mice, Rats
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