Murine glial protrusion transcripts predict localized Drosophila glial mRNAs involved in plasticity

TL;DR

This study shows that glial cells in fruit flies have localized mRNAs, similar to mammalian glia, which are important for synapse formation and may be linked to neurological diseases.

Contribution

The study identifies conserved localized glial transcripts in Drosophila and links them to synapse plasticity and neurological disease genes.

Findings

1,740 localized Drosophila glial transcripts were predicted using mammalian glial data.

Localized glial mRNAs are enriched for genes associated with neurological diseases.

Some localized glial transcripts are required for structural plasticity at neuromuscular junctions.

Abstract

Lee and Gala et al. meta-analyzed studies identifying mRNAs localized to cytoplasmic projections of various mammalian glial cells, which they showed are strong predictors of localized RNA in Drosophila and are associated with neurological diseases. They found some are essential for synapse formation in adjacent neurons.

The polarization of cells often involves the transport of specific mRNAs and their localized translation in distal projections. Neurons and glia are both known to contain long cytoplasmic processes, while localized transcripts have only been studied extensively in neurons, not glia, especially in intact nervous systems. Here, we predict 1,740 localized Drosophila glial transcripts by extrapolating from our meta-analysis of seven existing studies characterizing the localized transcriptomes and translatomes of synaptically associated mammalian glia. We demonstrate that the localization of mRNAs in mammalian glial projections strongly predicts the localization of their high-confidence Drosophila homologs in larval motor neuron–associated glial projections and are highly statistically enriched for genes associated with neurological diseases. We further show that some of these localized glial transcripts are specifically required in glia for structural plasticity at the nearby neuromuscular junction synapses. We conclude that peripheral glial mRNA localization is a common and conserved phenomenon and propose that it is likely to be functionally important in disease.

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