Apr 25, 2020

Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia

BioRxiv : the Preprint Server for Biology
N. J. Scott-HewittMichela Matteoli

Abstract

Neuronal circuits assembly requires the fine equilibrium between synapse formation and elimination. Microglia, through the elimination of supernumerary synapses, have an established role in this process. While the microglial receptor TREM2 and the soluble complement proteins C1q and C3 are recognized key players in this process, the neuronal molecular components that tag synapses to be eliminated are still undefined. Here we show that exposed phosphatidylserine (PS) represents a neuronal "eat-me" signal enabling microglial-mediated synapse pruning. In hippocampal neuron and microglia co-cultures, synapse elimination can be prevented by blocking accessibility of exposed PS using Annexin V or through microglial loss of TREM2. In vivo, exposed PS is detectable at both hippocampal and retinogeniculate synapses, where exposure coincides with the onset of synapse elimination and increased PS engulfment by microglia. Mice deficient in C1q, which fail to properly refine retinogeniculate connections, display elevated exposed PS and reduced PS engulfment by microglia. These data provide mechanistic insight into microglial-mediated synapse pruning and identify a novel role of developmentally regulated PS exposure that is common among deve...Continue Reading

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Mentioned in this Paper

Genome
Transcription Initiation Site
Transcription, Genetic
Spatial Distribution
Histocompatibility Testing
Poly A
Regulation of Transcription Factor Activity
Genomics
Donor Site
DDX53 gene

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