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http://purl.uniprot.org/citations/15620647http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15620647http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15620647http://www.w3.org/2000/01/rdf-schema#comment"

Background

Phagocytosis of cells undergoing apoptosis is essential during development, cellular turnover, and wound healing. Failure to promptly clear apoptotic cells has been linked to autoimmune disorders. C. elegans CED-12 and mammalian ELMO are evolutionarily conserved scaffolding proteins that play a critical role in engulfment from worm to human. ELMO functions together with Dock180 (a guanine nucleotide exchange factor for Rac) to mediate Rac-dependent cytoskeletal reorganization during engulfment and cell migration. However, the components upstream of ELMO and Dock180 during engulfment remain elusive.

Results

Here, we define a conserved signaling module involving the small GTPase RhoG and its exchange factor TRIO, which functions upstream of ELMO/Dock180/Rac during engulfment. Complementary studies in C. elegans show that MIG-2 (which we identify as the homolog of mammalian RhoG) and UNC-73 (the TRIO homolog) also regulate corpse clearance in vivo, upstream of CED-12. At the molecular level, we identify a novel set of evolutionarily conserved Armadillo (ARM) repeats within CED-12/ELMO that mediate an interaction with activated MIG-2/RhoG; this, in turn, promotes Dock180-mediated Rac activation and cytoskeletal reorganization.

Conclusions

The combination of in vitro and in vivo studies presented here identify two evolutionarily conserved players in engulfment, TRIO/UNC73 and RhoG/MIG-2, and the TRIO --> RhoG signaling module is linked by ELMO/CED-12 to Dock180-dependent Rac activation during engulfment. This work also identifies ARM repeats within CED-12/ELMO and their role in linking RhoG and Rac, two GTPases that function in tandem during engulfment."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.org/dc/terms/identifier"doi:10.1016/j.cub.2004.12.029"xsd:string
http://purl.uniprot.org/citations/15620647http://purl.org/dc/terms/identifier"doi:10.1016/j.cub.2004.12.029"xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Lu M."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Lu M."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Hengartner M.O."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Hengartner M.O."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Wu Y.C."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Wu Y.C."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Ravichandran K.S."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Ravichandran K.S."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Sondek J."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Sondek J."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Haney L.B."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Haney L.B."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Kinchen J.M."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Kinchen J.M."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Blangy A."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Blangy A."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Cheng L.C."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Cheng L.C."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Chou B.K."xsd:string
http://purl.uniprot.org/citations/15620647http://purl.uniprot.org/core/author"Chou B.K."xsd:string
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