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
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 108973 |
| Tidsskrift | Cell Reports |
| Vol/bind | 35 |
| Udgave nummer | 2 |
| Antal sider | 26 |
| ISSN | 2211-1247 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
We thank the staff at the Core Facility for Integrated Microscopy and Anders Bohl Pedersen for excellent technical assistance, and Kenneth Lindegaard Madsen for useful discussions. We thank Jeppe Cederholm Nielsen and Brian Thomas Devree for help with western blotting. We thank the Vienna Drosophila Resource Center, the Bloomington Stock Center, and the following colleagues for fly lines and reagents: Gábor Juhász, Stephan J. Sigrist, Thomas L. Schwarz, Pierre Leopold, Graeme W. Davis, Benjamin H. White, Edwin Levitan, Suzanne Eaton, Yuzuru Imai, Esteban C. Dell’Angelica, Jui-Chou Hsu, Paul Taghert, P. Shen, and Régis Giet. We acknowledge the respective communities for maintaining the Fiji and Inkscape software. This work was supported by Beckett-Fonden , Dagmar Marshalls Fond , Else og Mogens Wedell Wedellsborgs Fond , Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis Legat , Novo Nordisk Fonden , Torben og Alice Frimodts Fond , and by Aase og Ejnar Danielsens Fond .
Publisher Copyright:
© 2021 The Authors
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