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Gene Review

ELMO1  -  engulfment and cell motility 1

Homo sapiens

Synonyms: CED-12, CED12, ELMO-1, Engulfment and cell motility protein 1, KIAA0281, ...
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Disease relevance of ELMO1

  • On the other hand, we found that the expression of ELMO1 induces Rac activation in the plasmacytoma cells expressing DOCK2 but not ELMO1 [1].
  • HIV-1 Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis [2].
  • Furthermore, we show that ELMO, a key signaling molecule that participates in the phagocytosis of apoptotic cells, inhibited HIV transcription; however, knocking down endogenous ELMO expression in infected U937 cells rescued HIV transcription when these cells were coincubated with apoptotic targets [3].

High impact information on ELMO1

  • These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals [4].
  • Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2 [4].
  • The mechanism by which Dock180 or ELMO mediates Rac activation is not understood [5].
  • We found that DOCK2 associates with engulfment and cell motility (ELMO1) through its Src-homology 3 (SH3) domain [1].
  • These results indicate that the association of DOCK2 with ELMO1 is critical for DOCK2-mediated Rac activation, thereby suggesting that their association might be a therapeutic target for immunologic disorders caused by lymphocyte infiltration [1].

Biological context of ELMO1

  • Mutant forms of ELMO1 lacking these sites were defective in their ability to promote phagocytosis and migration in fibroblasts [6].
  • In this study, we used mass spectrometry to identify the following sites of ELMO1 phosphorylation: Tyr 18, Tyr 216, Tyr 511, Tyr 395, and Tyr 720 [6].
  • The cytotoxicity of ELMO, expressed as cell viability, was assessed using two independent endpoints: neutral red uptake (NRU) and the reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for MRC-5 fibroblasts and NRU for AGS cells [7].

Anatomical context of ELMO1

  • Subsequent in vitro analysis revealed that ELMO1 expression was elevated in cells cultured under high glucose conditions (25 mmol/l) compared with cells cultured under normal glucose conditions (5.5 mmol/l) [8].
  • In situ hybridization (ISH) using the kidney of normal and diabetic mice revealed that ELMO1 expression was weakly detectable mainly in tubular and glomerular epithelial cells in normal mouse kidney and was clearly elevated in the kidney of diabetic mice [8].
  • Interestingly, deletion mutants of ELMO1 missing their first 531 or first 330 amino acids that can still bind and cooperate with Dock180 in Rac activation failed to promote migration, which correlated with the inability to localize to lamellipodia [9].
  • ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex [10].
  • These data suggest that Dock180 is ubiquitylated on the plasma membrane, and also that Elmo1 functions as an inhibitor of ubiquitylation of Dock180 [11].

Associations of ELMO1 with chemical compounds

  • The binding of ELMO1 to Hck is specifically dependent on the interaction of a polyproline motif with the SH3 domain of Hck [12].
  • Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src-family kinase Hck [6].
  • ELMO functions together with Dock180 (a guanine nucleotide exchange factor for Rac) to mediate Rac-dependent cytoskeletal reorganization during engulfment and cell migration [13].
  • Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis [14].
  • The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor [15].

Physical interactions of ELMO1


Co-localisations of ELMO1


Regulatory relationships of ELMO1

  • DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1 [1].
  • We also found that ELMO1 regulated multiple Dock180 superfamily members to promote migration [9].
  • We conclude that RhoG activates Rac1 through Elmo and Dock180 to control cell morphology [15].
  • Membrane association of ELMO-Dock180 with ruffles were promoted when cells expressed an IpgB1-ELMO chimera, establishing that IpgB1 mimics the role of RhoG in producing membrane ruffles [17].

Other interactions of ELMO1


  1. DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. Sanui, T., Inayoshi, A., Noda, M., Iwata, E., Stein, J.V., Sasazuki, T., Fukui, Y. Blood (2003) [Pubmed]
  2. HIV-1 Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis. Janardhan, A., Swigut, T., Hill, B., Myers, M.P., Skowronski, J. PLoS Biol. (2004) [Pubmed]
  3. Signal transduction induced by apoptotic cells inhibits HIV transcription in monocytes/macrophages. Gekonge, B.N., Schiralli, G., Schlegel, R.A., Henderson, A.J. J. Leukoc. Biol. (2006) [Pubmed]
  4. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Gumienny, T.L., Brugnera, E., Tosello-Trampont, A.C., Kinchen, J.M., Haney, L.B., Nishiwaki, K., Walk, S.F., Nemergut, M.E., Macara, I.G., Francis, R., Schedl, T., Qin, Y., Van Aelst, L., Hengartner, M.O., Ravichandran, K.S. Cell (2001) [Pubmed]
  5. Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Brugnera, E., Haney, L., Grimsley, C., Lu, M., Walk, S.F., Tosello-Trampont, A.C., Macara, I.G., Madhani, H., Fink, G.R., Ravichandran, K.S. Nat. Cell Biol. (2002) [Pubmed]
  6. Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src-family kinase Hck. Yokoyama, N., deBakker, C.D., Zappacosta, F., Huddleston, M.J., Annan, R.S., Ravichandran, K.S., Miller, W.T. Biochemistry (2005) [Pubmed]
  7. Gastroprotective activity of a new semi-synthetic solidagenone derivative in mice. Rodríguez, J.A., Theoduloz, C., Sánchez, M., Yáñez, T., Razmilic, I., Schmeda-Hirschmann, G. J. Pharm. Pharmacol. (2005) [Pubmed]
  8. Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. Shimazaki, A., Kawamura, Y., Kanazawa, A., Sekine, A., Saito, S., Tsunoda, T., Koya, D., Babazono, T., Tanaka, Y., Matsuda, M., Kawai, K., Iiizumi, T., Imanishi, M., Shinosaki, T., Yanagimoto, T., Ikeda, M., Omachi, S., Kashiwagi, A., Kaku, K., Iwamoto, Y., Kawamori, R., Kikkawa, R., Nakajima, M., Nakamura, Y., Maeda, S. Diabetes (2005) [Pubmed]
  9. Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. Grimsley, C.M., Kinchen, J.M., Tosello-Trampont, A.C., Brugnera, E., Haney, L.B., Lu, M., Chen, Q., Klingele, D., Hengartner, M.O., Ravichandran, K.S. J. Biol. Chem. (2004) [Pubmed]
  10. Characterization of a novel interaction between ELMO1 and ERM proteins. Grimsley, C.M., Lu, M., Haney, L.B., Kinchen, J.M., Ravichandran, K.S. J. Biol. Chem. (2006) [Pubmed]
  11. Elmo1 inhibits ubiquitylation of Dock180. Makino, Y., Tsuda, M., Ichihara, S., Watanabe, T., Sakai, M., Sawa, H., Nagashima, K., Hatakeyama, S., Tanaka, S. J. Cell. Sci. (2006) [Pubmed]
  12. Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1. Scott, M.P., Zappacosta, F., Kim, E.Y., Annan, R.S., Miller, W.T. J. Biol. Chem. (2002) [Pubmed]
  13. Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. deBakker, C.D., Haney, L.B., Kinchen, J.M., Grimsley, C., Lu, M., Klingele, D., Hsu, P.K., Chou, B.K., Cheng, L.C., Blangy, A., Sondek, J., Hengartner, M.O., Wu, Y.C., Ravichandran, K.S. Curr. Biol. (2004) [Pubmed]
  14. Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Wang, X., Wu, Y.C., Fadok, V.A., Lee, M.C., Gengyo-Ando, K., Cheng, L.C., Ledwich, D., Hsu, P.K., Chen, J.Y., Chou, B.K., Henson, P., Mitani, S., Xue, D. Science (2003) [Pubmed]
  15. RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Katoh, H., Negishi, M. Nature (2003) [Pubmed]
  16. The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1. Santy, L.C., Ravichandran, K.S., Casanova, J.E. Curr. Biol. (2005) [Pubmed]
  17. Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery. Handa, Y., Suzuki, M., Ohya, K., Iwai, H., Ishijima, N., Koleske, A.J., Fukui, Y., Sasakawa, C. Nat. Cell Biol. (2007) [Pubmed]
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