Engulfment

Engulfment defective mutants on the right have many cell corpses compared to wild-type. Persistent cell corpses in embryos are marked with red arrows, whereas in adult worms with green arrows.

Clearance of apoptotic cells is of key importance during development, tissue homeostasis and wound healing in multi-cellular organisms. Genetic studies in the nematode Caenorhabditis elegans contributed remarkably to the understanding of the molecular regulation of apoptotic cell corpse clearance, also referred to as engulfment.

The understanding of apoptotic cell corpse clearance is of key importance. First, genetic studies showed that the molecules involved are evoutionarily highly conserved. Second, in higher organisms, it is known that defects in the engulfment can lead to autoimmune diseases (e.g. systemic lupus erythematosus), to chronic inflammation and impaird neuronal function. Additionally, the mechanism used for phagosome maturation is similar to the mechanism by which pathogenic bacteria (such as Mycobacterium tuberculosis) infect their host cells. Thus the knowledge gained from studies in the nematode are of key importance to multiple aspects of normal cellular homeostasis and disease.

People involved:

• Sheng Zeng

Selected publications:

Neukomm LJ, Zeng S, Frei AP, Huegli PA, Hengartner MO. Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans. Cell Death Differ. 2014 Jun;21(6):845-53

Martinez J, Almendinger J, Oberst A, Ness R, Dillon CP, Fitzgerald P, Hengartner MO, Green DR. Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells. PNAS 2011 Oct 18;108(42):17396-401.

Neukomm LJ, Frei AP, Cabello J, Kinchen JM, Zaidel-Bar R, Ma Z, Haney LB, Hardin J, Ravichandran KS, Moreno S, Hengartner MO:Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans.Nat Cell Biol. 2011 Jan;13:79-86.

Cabello J, Neukomm LJ, Günesdogan U, Burkart K, Charette SJ, Lochnit G, Hengartner MO, Schnabel R: The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac. PLoS Biol. 2010, 8: e1000297.

Kinchen JM, Doukoumetzidis K, Almendinger J, Stergiou L, Tosello-Trampont A, Sifri CD, Hengartner MO, Ravichandran KS: A pathway for phagosome maturation during engulfment of apoptotic cells. Nat Cell Biol 2008, 10:556-566.

Züllig S, Neukomm LJ, Jovanovic M, Charette SJ, Lyssenko NN, Halleck MS, Reutelingsperger CP, Schlegel RA, Hengartner MO: Aminophospholipid translocase TAT-1 promotes phosphatidylserine exposure during C. elegans apoptosis. Curr Biol 2007, 17:994-999.

Kinchen JM, Cabello J, Klingele D, Wong K, Feichtinger R, Schnabel H, Schnabel R, Hengartner MO: Two pathways converge at CED-10/Rac to mediate actin rearrangement and corpse removal in C. elegans. Nature 2005, 434:393-399.