Engulfment: ingestion and migration with Rac, Rho and TRIO
1National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. hensonp@njc.org
Abstract:
Apoptotic cells are removed from tissues by uptake mechanisms that depend on the GTPase Rac (CED-10 in C. elegans), which is activated by DOCK180/CED-5 in a trimolecular complex with ELMO/CED-12 and CrkII/CED-2. A study now identifies upstream components of this pathway in both worms and mammalian cells involving yet another GTPase, RhoG/MIG-2, and its activator TRIO/UNC-73.
Insights
Cellular debris removal relies on Rac GTPase, activated by DOCK180/CED-5, ELMO/CED-12, and CrkII/CED-2. This study reveals RhoG/MIG-2 and TRIO/UNC-73 as new upstream activators in worms and mammals.
Area of Science:
- Cell biology
- Molecular biology
- Developmental biology
Background:
- Apoptotic cell clearance is crucial for tissue homeostasis and preventing inflammation.
- The GTPase Rac (CED-10 in C. elegans) is a known key regulator of phagocytosis.
- Rac activation involves a trimolecular complex of DOCK180/CED-5, ELMO/CED-12, and CrkII/CED-2.
Purpose of the Study:
- To identify novel upstream regulators of the Rac-mediated apoptotic cell uptake pathway.
- To investigate the conserved roles of these regulators in both C. elegans and mammalian systems.
Main Methods:
- Genetic screening in C. elegans to identify mutants with defects in apoptotic cell corpse engulfment.
- Biochemical assays to confirm protein-protein interactions and GTPase activation.
- Cell-based assays in mammalian cell lines to validate findings.
Main Results:
- Identification of RhoG (MIG-2 in C. elegans) as a novel GTPase upstream of Rac in the engulfment pathway.
- Demonstration that TRIO/UNC-73 acts as the guanine nucleotide exchange factor (GEF) for RhoG/MIG-2.
- Conservation of the RhoG/MIG-2 and TRIO/UNC-73 pathway in mammalian cells for efferocytosis.
Conclusions:
- The pathway regulating apoptotic cell clearance is more complex than previously understood.
- RhoG GTPase, activated by TRIO, represents a new upstream component controlling Rac-mediated engulfment.
- This finding provides new targets for understanding and potentially modulating efferocytosis in disease.


