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First published online June 25, 2007
doi: 10.1242/10.1242/jcs.03463

Journal of Cell Science 120, 2143-2149 (2007)
Published by The Company of Biologists 2007
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Commentary

Journey to the grave: signaling events regulating removal of apoptotic cells

Jason M. Kinchen and Kodi S. Ravichandran*

Beirne Carter Center for Immunology Research, University of Virginia, 409 Lane Road, Charlottesville, VA 22908, USA

* Author for correspondence (e-mail: ravi{at}virginia.edu)

Accepted 19 April 2007

Programmed cell death is critical both for organ formation during development and during adult life, when billions of cells must be removed every day. The culmination of the apoptotic process is the specific recognition and engulfment of the apoptotic cell by a phagocyte. A number of recent studies have revealed a series of evolutionarily conserved proteins that link corpse recognition to membrane movement, facilitating the internalization of the target and its subsequent degradation. Two potential signaling modules have been identified: one involving the CED-12/ELMO and CED-5/Dock180 proteins, which function as a bipartite guanine nucleotide exchange factor (GEF) for Rac1, and a second involving CED-1/LRP1 (a potential engulfment receptor) and the adaptor protein CED-6/GULP. Recognition of the apoptotic cell modulates cytokine secretion by the phagocyte, resulting in an anti-inflammatory state distinct from that induced by necrotic cells. The recent molecular delineation of the phagocytic process and the identification of novel signaling proteins involved in engulfment have provided an exciting new platform for future studies into this biologically important process.

Key words: Engulfment, Apoptosis, GULP, ELMO, Doc 180, Rac, C. elegans




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