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

Sahil Nagpal; Karthikeyan Swaminathan; Daniel Beaudet; Maud Verdier; Samuel Wang; Christopher L. Berger; Florian Berger; Adam G. Hendricks

doi:10.1016/j.celrep.2024.114649

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

Sahil Nagpal, Karthikeyan Swaminathan, Daniel Beaudet, Maud Verdier, Samuel Wang, Christopher L. Berger, Florian Berger, Adam G. Hendricks^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	114649
Journal	Cell Reports
Volume	43
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2024.114649
Publication status	Published - 27 Aug 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Funding

We thank other students in the lab, namely Abdullah Chaudhary, Linda Balabanian, and Ora Cohen, for help with data analysis and thoughtful discussions. We also thank the Genome Quebec Innovation Centre at McGill for sequencing our DNA samples. The work was supported by Canadian Institutes of Health Research (CIHR) grants PJT-159490 and PJT-185997 to A.G.H.

Funders	Funder number
Canadian Institutes of Health Research	PJT-159490, PJT-185997
Canadian Institutes of Health Research

Keywords

CP: Cell biology
dynein
intracellular trafficking
kinesin
optogenetics

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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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AU - Wang, Samuel

AU - Berger, Christopher L.

AU - Berger, Florian

AU - Hendricks, Adam G.

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

Abstract

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Keywords

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