Local apoptotic-like mechanisms underlie complement-mediated synaptic pruning

Györffy, Balázs A. and Kun, Judit and Török, György and Bulyáki, Éva and Borhegyi, Zsolt and Gulyássy, Péter and Kis, Viktor and Szocsics, Péter and Micsonai, András and Matkó, János and Drahos, László and Juhász, Gábor and Kékesi, A. Katalin and Kardos, József (2018) Local apoptotic-like mechanisms underlie complement-mediated synaptic pruning. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115 (24). pp. 6303-6308. ISSN 0027-8424

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Abstract

C1q, a member of the immune complement cascade, is implicated in the selective pruning of synapses by microglial phagocytosis. C1q-mediated synapse elimination has been shown to occur during brain development, while increased activation and complement-dependent synapse loss is observed in neurodegenerative diseases. However, the molecular mechanisms underlying C1q-controlled synaptic pruning are mostly unknown. This study addresses distortions in the synaptic proteome leading to C1q-tagged synapses. Our data demonstrated the preferential localization of C1q to the presynapse. Proteomic investigation and pathway analysis of C1q-tagged synaptosomes revealed the presence of apoptotic-like processes in C1q-tagged synapses, which was confirmed experimentally with apoptosis markers. Moreover, the induction of synaptic apoptotic-like mechanisms in a model of sensory deprivation-induced synaptic depression led to elevated C1q levels. Our results unveiled that C1q label-based synaptic pruning is triggered by and directly linked to apoptotic-like processes in the synaptic compartment.

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