RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo

@article{Katoh2003RhoGAR,
  title={RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo},
  author={Hironori Katoh and Manabu Negishi},
  journal={Nature},
  year={2003},
  volume={424},
  pages={461-464}
}
The small GTPase Rac has a central role in regulating the actin cytoskeleton during cell migration and axon guidance. Elmo has been identified as an upstream regulator of Rac1 that binds to and functionally cooperates with Dock180 (refs 2–4). Dock180 does not contain a conventional catalytic domain for guanine nucleotide exchange on Rac, but possesses a domain that directly binds to and specifically activates Rac1 (refs 5, 6). The small GTPase RhoG mediates several cellular morphological… 

Figures from this paper

Exploring Rac GTPase regulation : the molecular mechanisms governing the DOCK180 and ELMO interaction and the role of this complex in Rac-mediated cell migration
TLDR
It is concluded that, at basal levels, ELMO/DOCK180 is complexed, with ELMO in an autoinhibited state in the cytosol, and proposed that the activation state of ELMO proteins is regulated, much like in Dia-family formins, via interaction with other proteins.
Activation of Rac1 by RhoG regulates cell migration
TLDR
RNA interference-mediated knockdown of RhoG in HeLa cells reduced cell migration in Transwell and scratch-wound migration assays and suggests that Rho G contributes to the regulation of Rac activity in migrating cells.
The Arf Family GTPase Arl4A Complexes with ELMO Proteins to Promote Actin Cytoskeleton Remodeling and Reveals a Versatile Ras-binding Domain in the ELMO Proteins Family*
TLDR
The present study identifies novel ELMO-interacting proteins to further define the molecular events capable of controlling ELMO recruitment to the membrane and concludes that ELMO contains a versatile RBD.
P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils
TLDR
It is shown that P-Rex1 also acts as a GEF for the Rac-related GTPase RhoG, both in vitro and in GPCR-stimulated primary mouse neutrophils, revealing a new signalling hierarchy in which P- Rex1 regulates Rac-dependent functions indirectly through RHoG-dependent recruitment of DOCK2.
ELMO 1 Directly Interacts with G βγ Subunit to Transduce GPCR Signaling to Rac 1 Activation in Chemotaxis
TLDR
The results suggest that chemokine GPCR-mediated interaction between Gβγ and ELMO1/Dock1 complex might serve as an evolutionarily conserved mechanism for Rac activation to regulate actin cytoskeleton for chemotaxis of human cells.
Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex
TLDR
This work identifies key conserved amino acids in the DHR-2 domain that are critical for the catalytic activity of Dock-GEFs (Dock1–4) and highlights a unique mechanism through which Dock- GEFs achieve spatial and temporal restriction of WAVE signaling.
Opening up on ELMO regulation
TLDR
It is proposed that the closed ELMO molecule masks protein-protein interfaces or domains with novel uncharacterized function; cell stimulation and GTPase binding to ELMO is proposed to activate (open) the protein and/or target the ELMO/DOCK180 complex to the cell membrane.
Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration
TLDR
It is found that constitutively active RhoG induced membrane ruffling via both Rac-dependent and -independent pathways and was important for Rac-independent cell migration, but did not significantly contribute to cell spreading even in these cells.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 27 REFERENCES
RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs.
TLDR
The data demonstrate that RhoG controls a pathway that requires the microtubule network and activates Rac1 and Cdc42Hs independently of their growth factor signaling pathways.
TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct activation of rhoG.
TLDR
It is demonstrated that Trio controls a signaling cascade that activates RhoG, which in turn activates Rac1 and Cdc42Hs, which strongly supports Rac1 not being activated by TrioD1 in vivo.
Integrin-mediated Signals Regulated by Members of the Rho Family of GTPases
TLDR
Several separable signaling pathways regulated by different members of the Rho family of GTPases converge to control adhesion-dependent changes in the organization of the cytoskeleton, changes that regulate cell morphology and behavior.
RhoG regulates gene expression and the actin cytoskeleton in lymphocytes
TLDR
Using effector domain mutants of RhoG, it is found that its ability to potentiate NFAT-dependent transcription correlates with its capacity to increase actin polymerization, supporting the suggestion that NFAT -dependent transcription is an actin-dependent process.
Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
TLDR
A domain within Dock180 is identified that specifically recognizes nucleotide-free Rac and can mediate GTP loading of Rac in vitro and it is proposed that the Dock180–ELMO complex functions as an unconventional two-part exchange factor for Rac.
Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity
TLDR
A novel protein domain is identified named DHR-2 (Dock Homology Region-2) that specifically binds to nucleotide-free Rac and activates Rac in vitro and in vivo and is suggested to be an evolutionarily conserved DOCK180-related superfamily of exchange factors.
Activation of Rac and Cdc42 by integrins mediates cell spreading.
TLDR
It is demonstrated that initial integrin-dependent activation of Rac and Cdc42 mediates cell spreading, suggesting that integrins activate at least one of these GTPases.
Activation of Rac1 by a Crk SH3-binding protein, DOCK180.
TLDR
The results strongly suggest that DOCK180 is a novel activator of Rac1 and involved in integrin signaling.
Small GTPase RhoG Is a Key Regulator for Neurite Outgrowth in PC12 Cells
TLDR
It is suggested that RhoG is a key regulator in NGF-induced neurite outgrowth, acting downstream of Ras and upstream of Rac1 and Cdc42 in PC12 cells.
...
1
2
3
...