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Cited by 13Microtubule and mitosis dynamicsCellular transport and secretionAutophagy in Disease and Therapy

Optogenetic control of kinesin-1, -2, -3 and dynein reveals their specific roles in vesicular transport

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Nagpal, Sahil, Swaminathan, Karthikeyan, Beaudet, Daniel, Verdier, Maud, Wang, Samuel, Berger, Christopher L., Berger, Florian, Hendricks, Adam G.·2024·Cell Reports
DOI 10.1016/j.celrep.2024.114649PMC PMC11416726

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Abstract

Each cargo in a cell employs a unique set of motor proteins for its transport. To dissect the roles of each type of motor, we developed optogenetic inhibitors of endogenous kinesin-1, -2, -3 and dynein motors and examined their effect on the transport of early endosomes, late endosomes, and lysosomes. While kinesin-1, -3, and dynein transport vesicles at all stages of endocytosis, kinesin-2 primarily drives late endosomes and lysosomes. Transient optogenetic inhibition of kinesin-1 or dynein causes both early and late endosomes to move more processively by relieving competition with opposing motors. Kinesin-2 and -3 support long-range transport, and optogenetic inhibition reduces the distances that their cargoes move. These results suggest that the directionality of transport is controlled through regulating kinesin-1 and dynein activity. On vesicles transported by several kinesin and dynein motors, modulating the activity of a single type of motor on the cargo is sufficient to direct motility.

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  • Kinesin-1 and kinesin-3 are major drivers of anterograde transport in axons, trafficking endosomes, lysosomes, mRNA, and other cargoes.

    “Kinesin-1 and kinesin-3 are major drivers of anterograde transport in axons, trafficking endosomes, lysosomes, mRNA, and other cargoes (Jenkins et al., 2012; Beaudet et al., 2024; Nagpal et al., 2024).”

    From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Nagpal et al., 2024

    The Discussion reports that kinesin-1 and kinesin-3 contribute to endosome and lysosome motility, and the Results describe their role in anterograde lysosome transport. The Introduction mentions mRNA transport by kinesins generally, but the paper does not establish that kinesin-1 and kinesin-3 are major drivers of mRNA trafficking specifically in axons. (LLM, conf=0.88)

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  • Teams of motors that transport cargo have distinct functions, including force-producing motors and others that act primarily as tethers.

    “teams of motors that transport cargo have distinct functions (Nagpal et al., 2024), including force-producing motors and others that act primarily as tethers”

    From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Nagpal et al., 2024

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Authors
Nagpal, S., Swaminathan, K., Beaudet, D., Verdier, M., Wang, S., Berger, C. L., Berger, F., & Hendricks, A. G.
Affiliations
  • McGill University (CA)
  • Université Paris-Est Créteil (FR)
  • University of Vermont (US)
  • Utrecht University (NL)
Corresponding author
Hendricks, Adam G.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2024-08
Volume
43
Issue
8
Pages
114649
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2024.114649
PMC
PMC11416726
OpenAlex
W4401677755
Cited by
13
References
4
Citations by year
2026: 7 · 2025: 4 · 2024: 2
FWCI
2.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • National Institutes of Health
  • Canadian Institutes of Health Research (PJT-159490, PJT-185997)
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
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
kinesin-1, kinesin-2, kinesin-3, dynein, vesicle trafficking, endosomes, lysosomes, optogenetic inhibition, long-range transport, endocytosis
MeSH terms
Animals, Biological Transport, Dyneins, Endocytosis, HeLa Cells, Humans, Lysosomes, Endosomes, Kinesins, Optogenetics

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