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    DRK/DOS/SOS Converge with Crk/Mbc/dCed-12 to Activate Rac1 during Glial Engulfment of Axonal Debris

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    Authors
    Lu, Tsai-yi
    Doherty, Johnna E.
    Freeman, Marc R.
    Student Authors
    Tsai-yi Lu; Johnna Doherty
    UMass Chan Affiliations
    Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program
    Graduate School of Biomedical Sciences, Neuroscience Program
    Freeman Lab
    Neurobiology
    Document Type
    Journal Article
    Publication Date
    2014-08-26
    Keywords
    Draper pathway
    Wallerian degeneration
    engulfment signaling
    reactive glia
    Molecular and Cellular Neuroscience
    
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    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-12has 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 glialresponses to axonal injury, and demonstrates a critical requirement for multiple GEFs in efficient glial activation after injury and internalization/degradation of axonal debris.
    Source
    Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12544-9. doi: 10.1073/pnas.1403450111. Epub 2014 Aug 6. Link to article on publisher's website
    DOI
    10.1073/pnas.1403450111
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/33338
    PubMed ID
    25099352
    Related Resources
    Link to article in PubMed
    Rights

    Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.

    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.1403450111
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    Morningside Graduate School of Biomedical Sciences Scholarly Publications
    Neurobiology Student Publications
    Neurobiology Faculty Publications

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