QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 8, 3180-3192, August 2007

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E07-02-0138v1 18/8/3180    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Venegas, V. Articles by Zhou, Z. Search for Related Content PubMed PubMed Citation Articles by Venegas, V. Articles by Zhou, Z.

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

Victor Venegas^*, and Zheng Zhou^*,

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

Submitted February 16, 2007; Revised May 22, 2007; Accepted May 31, 2007
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 Caenorhabditis elegans. Masking the surface phosphatidylserine inhibits apoptotic cell engulfment. CED-7, an ATP-binding cassette (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. Alternatively, phosphatidylserine exposure on apoptotic germ cells is not CED-7 dependent, but instead requires phospholipid scramblase PLSC-1, a homologue 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.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

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

Abbreviations used: ced, cell corpse-engulfment defective; MFG-E8, milk-fat-globule EGF8; PLSC, phospholipid scramblase; PS, phosphatidylserine.