Rab2 drives axonal transport of dense core vesicles and lysosomal organelles.

Autor:	Lund VK; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Lycas MD; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Schack A; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Andersen RC; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Gether U; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark., Kjaerulff O; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: okjaerulff@sund.ku.dk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Apr 13; Vol. 35 (2), pp. 108973.
DOI:	10.1016/j.celrep.2021.108973
Abstrakt:	Fast axonal transport of neuropeptide-containing dense core vesicles (DCVs), endolysosomal organelles, and presynaptic components is critical for maintaining neuronal functionality. How the transport of DCVs is orchestrated remains an important unresolved question. The small GTPase Rab2 mediates DCV biogenesis and endosome-lysosome fusion. Here, we use Drosophila to demonstrate that Rab2 also plays a critical role in bidirectional axonal transport of DCVs, endosomes, and lysosomal organelles, most likely by controlling molecular motors. We further show that the lysosomal motility factor Arl8 is required as well for axonal transport of DCVs, but unlike Rab2, it is also critical for DCV exit from cell bodies into axons. We also provide evidence that the upstream regulators of Rab2 and Arl8, Ema and BORC, activate these GTPases during DCV transport. Our results uncover the mechanisms underlying axonal transport of DCVs and reveal surprising parallels between the regulation of DCV and lysosomal motility. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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