RRC ID 31981
著者 Lu TY, Doherty J, Freeman MR.
タイトル DRK/DOS/SOS converge with Crk/Mbc/dCed-12 to activate Rac1 during glial engulfment of axonal debris.
ジャーナル Proc Natl Acad Sci U S A
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.
巻・号 111(34)
ページ 12544-9
公開日 2014-8-26
DOI 10.1073/pnas.1403450111
PII 1403450111
PMID 25099352
PMC PMC4151738
MeSH Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / physiology Animals Animals, Genetically Modified Axons / physiology Cytoskeletal Proteins / genetics Cytoskeletal Proteins / physiology Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / cytology* Drosophila melanogaster / genetics Drosophila melanogaster / physiology* Eye Proteins / genetics Eye Proteins / physiology* Genes, Insect Mutation Nerve Degeneration Neuroglia / physiology* Phagosomes / physiology Proto-Oncogene Proteins c-crk / genetics Proto-Oncogene Proteins c-crk / physiology Son of Sevenless Protein, Drosophila / genetics Son of Sevenless Protein, Drosophila / physiology* rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / physiology* ras Proteins / genetics ras Proteins / physiology
IF 9.412
引用数 15
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ショウジョウバエ 6033R-2 1044R-3