Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Jehle, A.W. et al.

Jehle, Gardai, Li, Linsel-Nitschke, Morimoto, Janssen, Vandivier, Wang, Greenberg, Dale, Qin, Henson, Tall,

ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages.

The mammalian ATP-binding cassette transporters A1 and A7 (ABCA1 and -A7) show sequence similarity to CED-7, a Caenorhabditis elegans gene that mediates the clearance of apoptotic cells. Using RNA interference or gene targeting, we show that knock down of macrophage ABCA7 but not -A1 results in defective engulfment of apoptotic cells. In response to apoptotic cells, ABCA7 moves to the macrophage cell surface and colocalizes with the low-density lipoprotein receptor-related protein 1 (LRP1) in phagocytic cups. The cell surface localization of ABCA7 and LRP1 is defective in ABCA7-deficient cells. C1q is an opsonin of apoptotic cells that acts via phagocyte LRP1 to induce extracellular signal-regulated kinase ( ERK) signaling. We show that ERK signaling is required for phagocytosis of apoptotic cells and that ERK phosphorylation in response to apoptotic cells or C1q is defective in ABCA7-deficient cells. These studies reveal a major role of ABCA7 and not -A1 in the clearance of apoptotic cells and therefore suggest that ABCA7 is an authentic orthologue of CED-7.[1]

References

ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages. Jehle, A.W., Gardai, S.J., Li, S., Linsel-Nitschke, P., Morimoto, K., Janssen, W.J., Vandivier, R.W., Wang, N., Greenberg, S., Dale, B.M., Qin, C., Henson, P.M., Tall, A.R. J. Cell Biol. (2006) [Pubmed]

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