ELMO-dependent Cell Signaling During Apoptotic Cell Engulfment and Cell Motility
Mammalian ELMO proteins (ELMO1-3, Engulfment and Cell Motility) are a family of evolutionarily conserved cytoplasmic adaptor proteins that function in concert with Dock proteins to promote the activation of the small GTPase Rac, a critical regulator of actin polymerization, cell shape and motility. The ELMO/Dock/Rac module plays an evolutionarily conserved role in the clearance of apoptotic cells and cell migration from nematodes to mammals. Analysis of ELMO1-deficient mice has revealed important roles for this protein in varied cell signaling processes, including apoptotic cell engulfment, in multiple tissues.
The overall goal of this project is to gain a better understanding of the molecular details of ELMO signaling in physiologically relevant contexts. There are several ongoing projects designed to address these questions. First, we would like a more detailed understanding of how ELMO proteins help cells integrate extracellular cues to affect cytoskeletal changes during phagocytosis and cell migration. Also, studies designed to assess unique and overlapping functions of the three mammalian ELMO family members will provide important clues into how the proteins function in vivo. Finally, by studying ELMO-dependent signaling in non-phagocytic cells, it may be possible to uncover novel signaling properties and a wider role for ELMO in regulating cellular activities.
Elliott MR, Zheng S, Park D, Woodson RI, Reardon MA, Juncadella IJ, Kinchen JM, Zhang J, Lysiak JJ and Ravichandran KS. Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature, 467:333 (2010).
- Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, Klibanov AL and Ravichandran KS. Brain-specific angiogenesis inhibitor 1 (BAI1) is a novel engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430 (2007).