Local apoptotic-like mechanisms underlie complementmediated synaptic pruning

Balázs A. Györffy, Judit Kun, György Török, Éva Bulyáki, Zsolt Borhegyi, Péter Gulyássy, Viktor Kis, Péter Szocsics, András Micsonai, János Matkó, László Drahos, Gábor Juhász, Katalin A. Kékesi, József Kardos

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17 Citations (Scopus)

Abstract

C1q, a member of the immune complement cascade, is implicated in the selective pruning of synapses by microglial phagocytosis. C1qmediated 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 C1qtagged 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.

Original languageEnglish
Pages (from-to)6303-6308
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number24
DOIs
Publication statusPublished - Jun 12 2018

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Keywords

  • Apoptotic-like mechanisms
  • Complement C1q
  • Proteomics
  • Synaptic pruning
  • Synaptosome sorting

ASJC Scopus subject areas

  • General

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