Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury

Mary Logan, Rachel Hackett, Johnna Doherty, Amy Sheehan, Sean Speese, Marc Freeman

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial responses to axon injury is molecularly encoded by unique isoforms of the Drosophila melanogaster engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Draper-II, an alternative splice variant, potently inhibits glial engulfment function. Draper-II suppresses Draper-I signaling through a previously undescribed immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain and the tyrosine phosphatase Corkscrew (Csw). Intriguingly, loss of Draper-II-Csw signaling prolongs expression of glial engulfment genes after axotomy and reduces the ability of glia to respond to secondary axotomy. Our work highlights a novel role for Draper-II in inhibiting glial responses to neurodegeneration, and indicates that a balance of opposing Draper-I and Draper-II signaling events is essential to maintain glial sensitivity to brain injury.

Original languageEnglish (US)
Pages (from-to)722-730
Number of pages9
JournalNature Neuroscience
Volume15
Issue number5
DOIs
StatePublished - May 2012

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Neuroglia
Axons
Wounds and Injuries
Axotomy
Tyrosine
Immunoreceptor Tyrosine-Based Activation Motif
Drosophila melanogaster
Phosphoric Monoester Hydrolases
Brain Injuries
Protein Isoforms
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury. / Logan, Mary; Hackett, Rachel; Doherty, Johnna; Sheehan, Amy; Speese, Sean; Freeman, Marc.

In: Nature Neuroscience, Vol. 15, No. 5, 05.2012, p. 722-730.

Research output: Contribution to journalArticle

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