APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development

A Piccini, E Castroflorio, Pierluigi Valente, FC Guarnieri, D Aprile, C Michetti, M Bramini, G Giansante, B Pinto, A Savardi, F Cesca, A Bachi, A Cattaneo, JD Wren, A Fassio, F Valtorta, Fabio Benfenati, S Giovedì

Research output: Contribution to journalArticle

Abstract

Synaptic transmission is critically dependent on synaptic vesicle (SV) recycling. Although the precise mechanisms of SV retrieval are still debated, it is widely accepted that a fundamental role is played by clathrin-mediated endocytosis, a form of endocytosis that capitalizes on the clathrin/adaptor protein complex 2 (AP2) coat and several accessory factors. Here, we show that the previously uncharacterized protein KIAA1107, predicted by bioinformatics analysis to be involved in the SV cycle, is an AP2-interacting clathrin-endocytosis protein (APache). We found that APache is highly enriched in the CNS and is associated with clathrin-coated vesicles via interaction with AP2. APache-silenced neurons exhibit a severe impairment of maturation at early developmental stages, reduced SV density, enlarged endosome-like structures, and defects in synaptic transmission, consistent with an impaired clathrin/AP2-mediated SV recycling. Our data implicate APache as an actor in the complex regulation of SV trafficking, neuronal development, and synaptic plasticity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)3596-3611
Number of pages16
JournalCell Reports
Volume21
Issue number12
DOIs
Publication statusPublished - 2017

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    Piccini, A., Castroflorio, E., Valente, P., Guarnieri, FC., Aprile, D., Michetti, C., Bramini, M., Giansante, G., Pinto, B., Savardi, A., Cesca, F., Bachi, A., Cattaneo, A., Wren, JD., Fassio, A., Valtorta, F., Benfenati, F., & Giovedì, S. (2017). APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development. Cell Reports, 21(12), 3596-3611. https://doi.org/10.1016/j.celrep.2017.11.073