ynaptic 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. Piccini et al. uncovered the AP2-interacting protein APache that acts in the clathrin-mediated endocytic machinery and synaptic vesicle trafficking. They found that silencing APache impairs neuronal development and neurotransmitter release during repetitive stimulation by markedly reducing vesicle recycling.

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

Benfenati, Fabio;Valtorta, Flavia;Pinto, Bruno Henrique;
2017

Abstract

ynaptic 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. Piccini et al. uncovered the AP2-interacting protein APache that acts in the clathrin-mediated endocytic machinery and synaptic vesicle trafficking. They found that silencing APache impairs neuronal development and neurotransmitter release during repetitive stimulation by markedly reducing vesicle recycling.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/91930
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