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Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases

Cason, Sydney E., Holzbaur, Erika L.F.·2023·Journal of Cell Biology
DOI 10.1083/jcb.202301084PMC PMC10620608

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Abstract

Neuronal autophagosomes form and engulf cargos at presynaptic sites in the axon and are then transported to the soma to recycle their cargo. Autophagic vacuoles (AVs) mature en route via fusion with lysosomes to become degradatively competent organelles; transport is driven by the microtubule motor protein cytoplasmic dynein, with motor activity regulated by a sequential series of adaptors. Using lysate-based single-molecule motility assays and live-cell imaging in primary neurons, we show that JNK-interacting proteins 3 (JIP3) and 4 (JIP4) are activating adaptors for dynein that are regulated on autophagosomes and lysosomes by the small GTPases ARF6 and RAB10. GTP-bound ARF6 promotes formation of the JIP3/4–dynein–dynactin complex. Either knockdown or overexpression of RAB10 stalls transport, suggesting that this GTPase is also required to coordinate the opposing activities of bound dynein and kinesin motors. These findings highlight the complex coordination of motor regulation during organelle transport in neurons.

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Metadata

Authors
Cason, S. E., & Holzbaur, E. L. F.
Affiliations
University of Pennsylvania 1 Department of Physiology, , Philadelphia, PA, USA
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2023-11-01
Volume
222
Issue
12
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.202301084
PMC
PMC10620608
Cited by
51
References
9
Language
en
Licence
Funders
National Institutes of Health (R35 GM126950)

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