Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse

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Abstract

Recycling of synaptic vesicles (SVs) is a fundamental step in the process of neurotransmission. Endocytosed SV can travel directly into the recycling pool or recycle through endosomes but little is known about the molecular actors regulating the switch between these SV recycling routes. ADP ribosylation factor 6 (Arf6) is a small GTPase known to participate in constitutive trafficking between plasma membrane and early endosomes. Here we have morphologically and functionally investigated Arf6-silenced hippocampal synapses and found an activity dependent accumulation of synaptic endosome-like organelles and increased release-competent docked SVs. These features were phenocopied by pharmacological blockage of Arf6 activation. The data reveal an unexpected role for this small GTPase in reducing the size of the readily releasable pool of SVs and in channeling retrieved SVs toward direct recycling rather than endosomal sorting. We propose that Arf6 acts at the presynapse to define the fate of an endocytosed SV.

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Erica Tagliatti

Center of SynapticNeuroscience, Fondazione Istituto Italiano di Tecnologia, Genova, Italy

Competing interests
The authors declare that no competing interests exist.
Manuela Fadda

Department of Experimental Medicine, University of Genova, Genova, Italy

Competing interests
The authors declare that no competing interests exist.
Antonio Falace

Institut national de la santé et de la recherche médicale, Institut de Neurobiologie de la Méditerranée, Marseille, France

Competing interests
The authors declare that no competing interests exist.
Fabio Benfenati

Center of SynapticNeuroscience, Fondazione Istituto Italiano di Tecnologia, Genova, Italy

Competing interests
The authors declare that no competing interests exist.
Anna Fassio

Center of SynapticNeuroscience, Fondazione Istituto Italiano di Tecnologia, Genova, Italy

For correspondence
afassio@unige.it

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experiments were carried out in accordance with the guidelines established by the European Communities Council (Directive 2010/63/EU of March 4th 2014) and were approved by the Italian Ministry of Health.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.