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The ATP binding cassette transporter ABC1, is required for the engulfment of corpses generated by apoptotic cell
1Centre d'Immunologie INSERM CNRS de Marseille-Luminy, 13288 Marseille Cedex 9, France.
Abstract:
ATP binding cassette (ABC) transporters define a family of proteins with strong structural similarities conserved across evolution and devoted to the translocation of a variety of substrates across cell membranes. A few members of the family are known in mammals, but although all of them are medically relevant proteins, knowledge of their molecular function remains scanty. We report here a morphological and functional study of the recently identified mammalian ABC transporter, ABC1. Its expression during embryonic development correlates spatially and temporally with the areas of programmed cell death. More specifically, ABC1 is expressed in macrophages engaged in the engulfment and clearance of dead cells. Moreover, ABC1 transporter is required for engulfment since the ability of macrophages to ingest apoptotic bodies is severely impaired after antibody-mediated steric blockade of ABC1. A structural homologue of ABC1 has been identified in the Caenorhabditis elegans genome and maps close to the ced-7 locus. Since ced-7 phenotype is precisely defined by an imparied engulfment of cell corpses, it is tempting to surmise that ABC1 might be a mammalian homologue of ced-7.
Insights
The mammalian ATP binding cassette (ABC) transporter, ABC1, is crucial for macrophages clearing dead cells during embryonic development. Impaired ABC1 function hinders the engulfment of apoptotic bodies, suggesting a role in programmed cell death clearance.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- ATP binding cassette (ABC) transporters are vital proteins involved in substrate translocation across cell membranes.
- While medically relevant, the molecular functions of many mammalian ABC transporters remain poorly understood.
Purpose of the Study:
- To investigate the morphological and functional roles of the newly identified mammalian ABC transporter, ABC1.
- To determine the involvement of ABC1 in embryonic development and cell death processes.
Main Methods:
- Studied ABC1 expression patterns during embryonic development.
- Examined the function of ABC1 in macrophage-mediated engulfment of apoptotic bodies using antibody-mediated blockade.
- Identified a structural homologue of ABC1 in Caenorhabditis elegans.
Main Results:
- ABC1 expression correlates spatially and temporally with programmed cell death sites during embryonic development.
- Macrophages expressing ABC1 are involved in clearing dead cells.
- Blocking ABC1 function severely impairs macrophage engulfment of apoptotic bodies.
- A structural homologue, potentially ced-7, was identified in C. elegans.
Conclusions:
- ABC1 plays a critical role in the engulfment and clearance of apoptotic cells by macrophages.
- ABC1 is essential for programmed cell death removal during embryonic development.
- ABC1 may be the mammalian homologue of the C. elegans ced-7 gene, highlighting conserved mechanisms in cell corpse engulfment.