Drosophila ELMO/CED-12 interacts with Myoblast city to direct myoblast fusion and ommatidial organization.
Members of the CDM (CED-5, Dock180, Myoblast city) superfamily of guanine nucleotide exchange factors function in diverse processes that include cell migration and myoblast fusion. Previous studies have shown that the SH3, DHR1 and DHR2 domains of Myoblast city (MBC) are essential for it to direct myoblast fusion in the Drosophila embryo, while the conserved DCrk-binding proline rich region is expendable. Herein, we describe the isolation of Drosophila ELMO/CED-12, an approximately 82 kDa protein with a pleckstrin homology (PH) and proline-rich domain, by interaction with the MBC SH3 domain. Mass spectrometry confirms the presence of an MBC/ELMO complex within the embryonic musculature at the time of myoblast fusion and embryos maternally and/or zygotically mutant for elmo exhibit defects in myoblast fusion. Overexpression of MBC and ELMO in the embryonic mesoderm causes defects in myoblast fusion reminiscent of those seen with constitutively-activated Rac1, supporting the previous finding that both the absence of and an excess of Rac activity are deleterious to myoblast fusion. Overexpression of MBC and ELMO/CED-12 in the eye causes perturbations in ommatidial organization that are suppressed by mutations in Rac1 and Rac2, demonstrating genetically that MBC and ELMO/CED-12 cooperate to activate these small GTPases in Drosophila.
Geisbrecht
Erika R
ER
Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, MO 64110, USA.
Haralalka
Shruti
S
Swanson
Selene K
SK
Florens
Laurence
L
Washburn
Mike P
MP
Abmayr
Susan M
SM
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002459:Cell Fusion; D002465:Cell Movement / Q000502:physiology*; D054910:Compound Eye, Arthropod / Q000196:embryology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000502:physiology*; D008648:Mesoderm / Q000196:embryology / Q000502:physiology; D009132:Muscles / Q000196:embryology / Q000502:physiology; D032446:Myoblasts / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D018909:src Homology Domains; D000097766:RAC2 GTP-Binding Protein
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D010750:Phosphoproteins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C521975:Ced-12 protein, Drosophila; C107441:mbc protein, Drosophila; C039077:platelet protein P47