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MBC in Press, published online ahead of print June 13, 2007
Mol. Biol. Cell 10.1091/mbc.E07-02-0138

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Submitted on February 16, 2007
Revised on May 22, 2007
Accepted on May 31, 2007

Two Alternative Mechanisms that Regulate the Presentation of Apoptotic-Cell Engulfment Signal in Caenorhabditis elegans

Victor Venegas* and Zheng Zhou*{dagger}

*Verna and Marrs McLean Department of Biochemistry and Molecular Biology, and {dagger}Program of Developmental Biology, Baylor College of Medicine, Houston, TX 77030

Monitoring Editor: Donald Newmeyer

Phosphatidylserine exposed on the surface of apoptotic mammalian cells is considered an "eat me" signal that attracts phagocytes. The generality of using phosphatidylserine as a clearance signal for apoptotic cells in animals and the regulation of this event remain uncertain. Using ectopically expressed mouse MFG-E8, a secreted phosphatidylserine-binding protein, we detected specific exposure of phosphatidylserine on the surface of apoptotic cells in C. elegans. Masking the surface phosphatidylserine inhibits apoptotic cell-engulfment. CED-7, an ABC transporter, is necessary for the efficient exposure of phosphatidylserine on apoptotic somatic cells, and for the recognition of these cells by phagocytic receptor CED-1. On the other hand, phosphatidylserine exposure on apoptotic germ cells is not CED-7-dependent, but instead requires PLSC-1, a homolog of mammalian phospholipid scramblases. Moreover, deleting plsc-1 results in the accumulation of apoptotic germ cells but not apoptotic somatic cells. These observations suggest that phosphatidylserine might be recognized by CED-1 and act as a conserved "eat me" signal from nematodes to mammals. Furthermore, the two different biochemical activities used in somatic cells (ABC transporter) and germ cells (phospholipid scramblase) suggest an increased complexity in the regulation of phosphatidylserine presentation in response to apoptotic signals in different tissues and during different developmental stages.

Address correspondence to: Zheng Zhou (zhengz{at}bcm.tmc.edu)




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