Rab2 drives axonal transport of dense core vesicles and lysosomal organelles
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Rab2 drives axonal transport of dense core vesicles and lysosomal organelles. / Lund, Viktor Karlovich; Lycas, Matthew Domenic; Schack, Anders; Andersen, Rita Chan; Gether, Ulrik; Kjaerulff, Ole.
In: Cell Reports, Vol. 35, No. 2, 108973, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rab2 drives axonal transport of dense core vesicles and lysosomal organelles
AU - Lund, Viktor Karlovich
AU - Lycas, Matthew Domenic
AU - Schack, Anders
AU - Andersen, Rita Chan
AU - Gether, Ulrik
AU - Kjaerulff, Ole
N1 - Publisher Copyright: © 2021 The Authors
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Arl8
KW - axonal transport
KW - dense core vesicles
KW - Drosophila
KW - endosomes
KW - lysosomes
KW - membrane trafficking
KW - neuropeptides
KW - Rab2
KW - synaptogenesis
U2 - 10.1016/j.celrep.2021.108973
DO - 10.1016/j.celrep.2021.108973
M3 - Journal article
C2 - 33852866
AN - SCOPUS:85104084528
VL - 35
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 2
M1 - 108973
ER -
ID: 262938831