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Lookup NU author(s): Dr Julien Peltier, Professor Matthias TrostORCiD
This is the final published version of an article that has been published in its final definitive form by National Academy of Sciences, 2018.
For re-use rights please refer to the publisher's terms and conditions.
© 2018 National Academy of Sciences. All rights reserved. Activity-dependent bulk endocytosis (ADBE) is the dominant mode of synaptic vesicle endocytosis during high-frequency stimulation, suggesting it should play key roles in neurotransmission during periods of intense neuronal activity. However, efforts in elucidating the physiological role of ADBE have been hampered by the lack of identified molecules which are unique to this endocytosis mode. To address this, we performed proteomic analysis on purified bulk endosomes, which are a key organelle in ADBE. Bulk endosomes were enriched via two independent approaches, a classical subcellular fractionation method and isolation via magnetic nanoparticles. There was a 77% overlap in proteins identified via the two protocols, and these molecules formed the ADBE core proteome. Bioinformatic analysis revealed a strong enrichment in cell adhesion and cytoskeletal and signaling molecules, in addition to expected synaptic and trafficking proteins. Network analysis identified Rab GTPases as a central hub within the ADBE proteome. Subsequent investigation of a subset of these Rabs revealed that Rab11 both facilitated ADBE and accelerated clathrin-mediated endocytosis. These findings suggest that the ADBE proteome will provide a rich resource for the future study of presynaptic function, and identify Rab11 as a regulator of presynaptic function.
Author(s): Kokotos AC, Peltier J, Davenport EC, Trost M, Cousin MA
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
Year: 2018
Volume: 115
Issue: 43
Pages: E10177-E10186
Online publication date: 09/10/2018
Acceptance date: 13/09/2018
Date deposited: 26/11/2018
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: https://doi.org/10.1073/pnas.1809189115
DOI: 10.1073/pnas.1809189115
PubMed id: 30301801
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