Molecular motor function in axonal transport in vivo probed by genetic and computational analysis in Drosophila
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Bidirectional axonal transport driven by kinesin and dynein along microtubules is critical to neuronal viability and function. To evaluate axonal transport mechanisms, we developed a high-resolution imaging system to track the movement of amyloid precursor protein (APP) vesicles in Drosophila segmental nerve axons. Computational analyses of a large number of moving vesicles in defined genetic backgrounds with partial reduction or overexpression of motor proteins enabled us to test with high precision existing and new models of motor activity and coordination in vivo. We discovered several previously unknown features of vesicle movement, including a surprising dependence of anterograde APP vesicle movement velocity on the amount of kinesin-1. This finding is largely incompatible with the biophysical properties of kinesin-1 derived from in vitro analyses. Our data also suggest kinesin-1 and cytoplasmic dynein motors assemble in stable mixtures on APP vesicles and their direction and velocity are controlled at least in part by dynein intermediate chain.
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In Drosophila, interactions between KLC and dynein intermediate chain are important in the switch between plus and minus end-directed movement.
“Similar results have been found in a study of kinesin-1 transport of amyloid precursor protein along axons in Drosophila; in this study, it appeared that interactions between KLC and dynein intermediate chain are important in the switch between plus and minus end–directed movement (Reis et al., 2012).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Reis et al., 2012
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Self-citation
- Authors
- Reis, G. F., Yang, G., Szpankowski, L., Weaver, C., Shah, S. B., Robinson, J. T., Hays, T. S., Danuser, G., & Goldstein, L. S. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Scripps Research Institute (US)
- University of California San Diego (US)
- University of Minnesota (US)
- Corresponding author
- Goldstein, Lawrence S. B.
- ORCID
- Venue
- Molecular Biology of the Cell
- Published
- 2012-05
- Volume
- 23
- Issue
- 9
- Pages
- 1700-1714
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC3338437
- OpenAlex
- W2122261008
- Cited by
- 80
- References
- 87
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 10 · 2014: 13 · 2013: 12 · 2012: 7
- FWCI
- 6.37
- 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)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (GM067230)
- National Institute on Aging (NRSA-5F31AG024672, R01AG032180, AG032180, F31AG024672)
- National Institute of General Medical Sciences (U01GM067230, GM 35252, R01GM044757, R01GM035252, T32GM007198)
- National Institute of Child Health and Human Development
- Topics
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- axonal transport, kinesin-1, cytoplasmic dynein, dynein intermediate chain, microtubules, anterograde transport
- MeSH terms
- Dynactin Complex, Animals, Axonal Transport, Biological Transport, Drosophila, Dyneins, Microtubule-Associated Proteins, Motor Activity, Kinesins, Amyloid beta-Protein Precursor, Computational Biology, Transport Vesicles, Drosophila Proteins
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