Publications (2)17.59 Total impact
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Article: Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance.
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ABSTRACT: Generation of spermatozoa involves segregation of most of the cytoplasm into residual bodies, which are detached from spermatids and eliminated in mammals. However, the molecular and cellular mechanism underlying the removal of residual bodies remains largely unknown. Here, we demonstrate that during C. elegans spermatogenesis residual bodies are engulfed and degraded by gonadal sheath cells, a process that uses the same set of genes underlying apoptotic cell removal. The two partially redundant engulfment pathways that clear cell corpses also mediate phagocytosis of residual bodies, possibly by recognizing the 'eat me' signal phosphatidylserine exposed on the surface. The residual body-containing phagosome undergoes a maturation process involving sequential steps including dynamic coating with PtdIns(3)P and association of RAB small GTPases. The genetic hierarchy of residual body removal in hermaphrodites is similar to that of cell corpse clearance, but male residual body removal involves a distinct hierarchy, with differential use of the engulfment genes. Efficient removal of residual bodies regulates the number of spermatids and effective transfer of spermatids during male matings. Our results indicate that a similar molecular mechanism is employed for the removal of residual bodies and apoptotic cell corpses in C. elegans.Development 12/2012; 139(24):4613-22. · 6.60 Impact Factor -
Article: C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on phagocytes for cell corpse engulfment.
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ABSTRACT: During programmed cell death, apoptotic cells are rapidly removed by phagocytes. How dying cells are recognized remains poorly understood. Here we identify a secreted lipid transfer/LPS-binding family protein, NRF-5, which is required for efficient clearance of cell corpses. We observed that phosphatidylserine (PS), which is externalized to the outer leaflet of plasma membranes in apoptotic cells, is also detected on the surface of engulfing cells. Loss of NRF-5 function completely blocks PS appearance on engulfing cells but causes accumulation of PS on apoptotic cells, a phenotype observed in both ced-7(lf) and ttr-52(lf) mutants. The NRF-5 protein is expressed in and secreted from body wall muscle cells and clusters around apoptotic cells in a CED-7-dependent manner. NRF-5 associates with TTR-52, binds PS, and displays lipid transfer activity in vitro. Our data suggest that NRF-5 may act with CED-7 and TTR-52 to mediate PS transfer from apoptotic cells to engulfing cells and thus promotes engulfment by phagocytes.Current biology: CB 06/2012; 22(14):1276-84. · 10.99 Impact Factor
