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Opposing functions for retromer and Rab11 in extracellular vesicle cargo traffic at synapses

Rylie B. Walsh, Agata N. Becalska, Matthew J. Zunitch, ShiYu Wang, Berith Isaac, Anna Yeh, Kate Koles, View ORCID ProfileAvital A. Rodal
doi: https://doi.org/10.1101/645713
Rylie B. Walsh
Department of Biology, Brandeis University, Waltham, MA 02453
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Agata N. Becalska
Department of Biology, Brandeis University, Waltham, MA 02453
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Matthew J. Zunitch
Department of Biology, Brandeis University, Waltham, MA 02453
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ShiYu Wang
Department of Biology, Brandeis University, Waltham, MA 02453
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Berith Isaac
Department of Biology, Brandeis University, Waltham, MA 02453
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Anna Yeh
Department of Biology, Brandeis University, Waltham, MA 02453
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Kate Koles
Department of Biology, Brandeis University, Waltham, MA 02453
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Avital A. Rodal
Department of Biology, Brandeis University, Waltham, MA 02453
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  • ORCID record for Avital A. Rodal
  • For correspondence: arodal@brandeis.edu
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Abstract

Neuronal extracellular vesicles (EVs) play critical roles in intercellular communication and in propagation of pathogenic proteins in neurological disease. However, little is known about how cargoes are selectively packaged into neuronal EVs. Here, we examined the intracellular traffic and release of the EV cargoes Amyloid Precursor Protein (APP) and Synaptotagmin-4 (Syt4) at presynaptic nerve terminals of Drosophila motor neurons. We found that loss of the endosomal retromer complex leads to increased EV cargo levels both presynaptically and in EVs, and that this function is separable from previously identified roles of neuronal retromer. Conversely, EV cargo levels are reduced in rab11 mutants, and EV cargo sorting depends on a balance between Rab11-mediated recycling and retromer-dependent removal from the EV pathway. Rab11 and retromer have previously been implicated in Alzheimer’s Disease, suggesting that these competing pathways may serve as therapeutic targets for limiting accumulation and release of toxic EV cargoes.

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Posted May 21, 2019.
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Opposing functions for retromer and Rab11 in extracellular vesicle cargo traffic at synapses
Rylie B. Walsh, Agata N. Becalska, Matthew J. Zunitch, ShiYu Wang, Berith Isaac, Anna Yeh, Kate Koles, Avital A. Rodal
bioRxiv 645713; doi: https://doi.org/10.1101/645713
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Opposing functions for retromer and Rab11 in extracellular vesicle cargo traffic at synapses
Rylie B. Walsh, Agata N. Becalska, Matthew J. Zunitch, ShiYu Wang, Berith Isaac, Anna Yeh, Kate Koles, Avital A. Rodal
bioRxiv 645713; doi: https://doi.org/10.1101/645713

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