title: Characterization of a novel interaction between ELMO1 and ERM proteins.
abstract: ERMs are closely related proteins involved in cell migration, cell adhesion, maintenance of cell shape, and formation of microvilli through their ability to cross-link the plasma membrane with the actin cytoskeleton. ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex. Here we showed that ERM proteins associate directly with ELMO1 as purified recombinant proteins in vitro and at endogenous levels in intact cells. We mapped ERM binding on ELMO1 to the N-terminal 280 amino acids, which overlaps with the region required for binding to the GTPase RhoG, but is distinct from the C-terminal Dock180 binding region. Consistent with this, ELMO1 could simultaneously bind both radixin and Dock180, although radixin did not alter Rac activation via the Dock180-ELMO complex. Most interestingly, radixin binding did not affect ELMO binding to active RhoG and a trimeric complex of active RhoG-ELMO-radixin could be detected. Moreover, the three proteins colocalized at the plasma membrane. Finally, in contrast to most other ERM-binding proteins, ELMO1 binding occurred independently of the state of radixin C-terminal phosphorylation, suggesting an ELMO1 interaction with both the active and inactive forms of ERM proteins and implying a possible role of ELMO in localizing or retaining ERM proteins in certain cellular sites. Together these data suggest that ELMO1-mediated cytoskeletal changes may be coordinated with ERM protein crosslinking activity during dynamic cellular functions.
authors.affiliation: Beirne Carter Center for Immunology Research, and Department of Microbiology, University of Virginia, Lane Road, Charlottesville, VA 22903, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Grimsley
authors.forename: Mingjian
authors.initials: M
authors.lastname: Lu
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Haney
authors.forename: Jason M
authors.initials: JM
authors.lastname: Kinchen
authors.forename: Kodi S
authors.initials: KS
authors.lastname: Ravichandran
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C099818:DOCK1 protein, human; C465214:ELMO1 protein, human; C510359:ELMO1 protein, mouse; C086680:ETV5 protein, human; C513242:Etv5 protein, mouse; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C071776:radixin; C075397:RHOG protein, human; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins