Cell ReportsArticleAPache Is an AP2-Interacting Protein Involvedin Synaptic Vesicle Traffickingand Neuronal DevelopmentAlessandra Piccini,1Enrico Castroflorio,2Pierluigi Valente,1Fabrizia C. Guarnieri,3Davide Aprile,1Caterina Michetti,2Mattia Bramini,2Giorgia Giansante,1Bruno Pinto,4,5Annalisa Savardi,1,4Fabrizia Cesca,2Angela Bachi,6Angela Cattaneo,6Jonathan D. Wren,7Anna Fassio,1,2Flavia Valtorta,3Fabio Benfenati,1,2,8,*and Silvia Giovedı`1,8,9,*1Department of Experimental Medicine, University of Genova, 16132 Genova, Italy2Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, 16132 Genova, Italy3San Raffaele Scientific Institute and Vita Salute University, 20132 Milano, Italy4Local Micro-environment and Brain Development Laboratory, Istituto Italiano di Tecnologia, 16163 Genova, Italy5Bio@SNS, Scuola Normale Superiore, 56126 Pisa, Italy6IFOM, FIRC Institute of Molecular Oncology, 20132 Milano, Italy7Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104-5005, USA8These authors contributed equally9Lead Contact*Correspondence:fabio.benfenati@iit.it(F.B.),silvia.giovedi@unige.it(S.G.)https://doi.org/10.1016/j.celrep.2017.11.073SUMMARYSynaptic transmission is critically dependent on syn-aptic vesicle (SV) recycling. Although the precisemechanisms of SV retrieval are still debated, it iswidely accepted that a fundamental role is playedby clathrin-mediated endocytosis, a form of endocy-tosis that capitalizes on the clathrin/adaptor proteincomplex 2 (AP2) coat and several accessory factors.Here, we show that the previously uncharacterizedprotein KIAA1107, predicted by bioinformatics anal-ysis to be involved in the SV cycle, is an AP2-interact-ing clathrin-endocytosis protein (APache). We foundthat APache is highly enriched in the CNS and isassociated with clathrin-coated vesicles via interac-tion with AP2. APache-silenced neurons exhibit asevere impairment of maturation at early develop-mental stages, reduced SV density, enlarged endo-some-like structures, and defects in synaptictransmission, consistent with an impaired clathrin/AP2-mediated SV recycling. Our data implicateAPache as an actor in the complex regulation ofSV trafficking, neuronal development, and synapticplasticity.

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

Piccini A;Castroflorio E;Valente P;Aprile D;GIANSANTE, GIORGIA;SAVARDI, ANNALISA;Cesca F;Bachi A;Fassio A;Valtorta F;Benfenati F;Giovedì S.
2017

Abstract

Cell ReportsArticleAPache Is an AP2-Interacting Protein Involvedin Synaptic Vesicle Traffickingand Neuronal DevelopmentAlessandra Piccini,1Enrico Castroflorio,2Pierluigi Valente,1Fabrizia C. Guarnieri,3Davide Aprile,1Caterina Michetti,2Mattia Bramini,2Giorgia Giansante,1Bruno Pinto,4,5Annalisa Savardi,1,4Fabrizia Cesca,2Angela Bachi,6Angela Cattaneo,6Jonathan D. Wren,7Anna Fassio,1,2Flavia Valtorta,3Fabio Benfenati,1,2,8,*and Silvia Giovedı`1,8,9,*1Department of Experimental Medicine, University of Genova, 16132 Genova, Italy2Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, 16132 Genova, Italy3San Raffaele Scientific Institute and Vita Salute University, 20132 Milano, Italy4Local Micro-environment and Brain Development Laboratory, Istituto Italiano di Tecnologia, 16163 Genova, Italy5Bio@SNS, Scuola Normale Superiore, 56126 Pisa, Italy6IFOM, FIRC Institute of Molecular Oncology, 20132 Milano, Italy7Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104-5005, USA8These authors contributed equally9Lead Contact*Correspondence:fabio.benfenati@iit.it(F.B.),silvia.giovedi@unige.it(S.G.)https://doi.org/10.1016/j.celrep.2017.11.073SUMMARYSynaptic transmission is critically dependent on syn-aptic vesicle (SV) recycling. Although the precisemechanisms of SV retrieval are still debated, it iswidely accepted that a fundamental role is playedby clathrin-mediated endocytosis, a form of endocy-tosis that capitalizes on the clathrin/adaptor proteincomplex 2 (AP2) coat and several accessory factors.Here, we show that the previously uncharacterizedprotein KIAA1107, predicted by bioinformatics anal-ysis to be involved in the SV cycle, is an AP2-interact-ing clathrin-endocytosis protein (APache). We foundthat APache is highly enriched in the CNS and isassociated with clathrin-coated vesicles via interac-tion with AP2. APache-silenced neurons exhibit asevere impairment of maturation at early develop-mental stages, reduced SV density, enlarged endo-some-like structures, and defects in synaptictransmission, consistent with an impaired clathrin/AP2-mediated SV recycling. Our data implicateAPache as an actor in the complex regulation ofSV trafficking, neuronal development, and synapticplasticity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/886784
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