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Activity-dependent bulk endocytosis proteome reveals a key presynaptic role for the monomeric GTPase Rab11

Lookup NU author(s): Dr Julien Peltier, Professor Matthias Trost

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This is the final published version of an article that has been published in its final definitive form by National Academy of Sciences, 2018.

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Abstract

© 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.


Publication metadata

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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