PAT-2/ α Integrin Defines a Novel Engulfment Pathway Acting Predominantly in Muscle Cells
Date Issued
2008
Date
2008
Author(s)
Hsieh, Hsiao-Han
Abstract
Integrins are heterodimeric transmembrane receptors that function in cell adhesion, migration, cell cycle progression, differentiation and apoptosis. Its role in the phagocytosis of apoptotic cells has been shown in cultured mammalian cells but has not yet been characterized in vivo. There are two α subunits, PAT-2 and INA-1, and a sole β subunit, PAT-3, in C. elegans. PAT-2 is known to be essential for sarcomere assembly and pat-2 mutants arrested at the 2-fold stage when active muscle movements start. We found that in pat-2 loss-of -function embryos the number of cell corpses significantly increased when compared with that of wild type. A time-lapse microscopic recording showed that the increase of cell corpse number in the pat-2(st567) embryos was due to the failure of cell-corpse removal. C. elegans cell-corpse engulfment was previously shown to be mediated by two partially redundant pathways, ced-1, ced-6, ced-7 in one and ced-2, ced-5 and ced-12 in the other. Clustering of PAT-2 around cell corpses was not affected by ced-1 or ced-5 mutation. In addition, the pat-2 mutation further enhanced the single mutants or double mutants between the two pathways, suggesting that pat-2 may function in a third engulfment pathway. Like pat-2, other genes involved in the body wall muscle assembly also function of cell-corpse engulfment, likely in the same pathway with pat-2. Muscle-specific expression of pat-2 rescued the corpse-engulf-defect of pat-2 embryos. This result indicates that muscle cells, at least primarily, act as engulfing cells in the PAT-2-mediated engulfment process. We conclude that PAT-2 integrin defines a novel engulfment pathway in muscle cells.
Subjects
programmed cell death
cell corpse
engulfment
C. elegans
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