Cited by 80Microtubule and mitosis dynamicsCellular transport and secretionHereditary Neurological Disorders

Molecular motor function in axonal transport in vivo probed by genetic and computational analysis in Drosophila

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Reis, Gerald F., Yang, Ge, Szpankowski, Lukasz, Weaver, Carole, Shah, Sameer B., Robinson, John T., Hays, Thomas S., Danuser, Gaudenz +1 more·2012·Molecular Biology of the Cell

Abstract

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).”

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  1. Theodoridis S Koutroumbas K Pattern Recognition 2009 4th ed. Burlington, MA Elsevier

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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.
Venue
Molecular Biology of the Cell
Published
2012-05
Volume
23
Issue
9
Pages
1700-1714
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
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
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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