DRK/DOS/SOS converge with Crk/Mbc/dCed-12 to activate Rac1 during glial engulfment of axonal debris

Tsai Yi Lu, Johnna Doherty, Marc Freeman

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Nervous system injury or disease leads to activation of glia, which govern postinjury responses in the nervous system. Axonal injury in Drosophila results in transcriptional up-regulation of the glial engulfment receptor Draper; there is extension of glial membranes to the injury site (termed activation), and then axonal debris is internalized and degraded. Loss of the small GTPase Rac1 from glia completely suppresses glial responses to injury, but upstream activators remain poorly defined. Loss of the Rac guanine nucleotide exchange factor (GEF) Crk/myoblast city (Mbc)/dCed-12 has no effect on glial activation, but blocks internalization and degradation of debris. Here we show that the signaling molecules downstream of receptor kinase (DRK) and daughter of sevenless (DOS) (mammalian homologs, Grb2 and Gab2, respectively) and the GEF son of sevenless (SOS) (mammalian homolog, mSOS) are required for efficient activation of glia after axotomy and internalization/degradation of axonal debris. At the earliest steps of glial activation, DRK/DOS/SOS function in a partially redundant manner with Crk/Mbc/dCed-12, with blockade of both complexes strongly suppressing all glial responses, similar to loss of Rac1. This work identifies DRK/DOS/SOS as the upstream Rac GEF complex required for glial responses to axonal injury, and demonstrates a critical requirement for multiple GEFs in efficient glial activation after injury and internalization/degradation of axonal debris.

Original languageEnglish (US)
Pages (from-to)12544-12549
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number34
DOIs
StatePublished - Aug 26 2014
Externally publishedYes

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Myoblasts
Neuroglia
Phosphotransferases
Guanine Nucleotide Exchange Factors
Wounds and Injuries
Nervous System Trauma
Axotomy
Monomeric GTP-Binding Proteins
Nervous System Diseases
Nervous System
Drosophila
Up-Regulation

Keywords

  • Draper pathway
  • Engulfment signaling
  • Reactive glia
  • Wallerian degeneration

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

DRK/DOS/SOS converge with Crk/Mbc/dCed-12 to activate Rac1 during glial engulfment of axonal debris. / Lu, Tsai Yi; Doherty, Johnna; Freeman, Marc.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 34, 26.08.2014, p. 12544-12549.

Research output: Contribution to journalArticle

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