Employing combinatory approaches of genetics, cell biology and biochemistry, we have been systemically identifying new genes and dissecting regulatory mechanisms controlling various aspects of apoptotic cell removal including recognition, internalization and degradation of cell corpses. Among them, TTR-52 and NRF-5 are bridging molecules that mediate recognition of cell corpses (Wang et al.,Nat Cell Biol2010; Zhang et al.,Curr Biol2012; Kang et al.,Genes Dev.2012). Myotubularin phosphatase MTM-1 coordinates with PI3 kinases PIKI-1 and VPS-34 to control initiation and completion of cell corpse engulfment (Zou et al.,PLos Genet2009; Cheng et al.,JCB2015, Liu et al.,JCB2018). Multiple Rab GTPases coordinate to regulate phagosome maturation and lysosomal degradation of apoptotic cells (Lu et al.,Development2008; Li et al.,Development2009; Guo et al.,PNAS2010, Yin et al.,JCB2017). Moreover, we found that non-apoptotic targets like residual bodies generated during spermatogenesis are recognized and cleared by the same molecular machinery that removes apoptotic cells (Huang et al.,Development2012). In addition, we demonstrate that the autophagy pathway contributes to cell corpse clearance through the PI3 kinase VPS-34(Cheng et al.,Autophagy2013). These findings have greatly advanced our understanding of how apoptotic cells are properly removed via the lysosome-dependent degradation pathways. Our current and planned research will focus on the regulatory machinery controlling cell corpse degradation. As evolutionarily conserved mechanisms are utilized to remove apoptotic cells, our studies inC. eleganswill deepen our understanding of this key process in both worms and mammals.
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Employing combinatory approaches of genetics, cell biology and biochemistry, we have been systemically identifying new genes and dissecting regulatory mechanisms controlling various aspects of apoptotic cell removal including recognition, internalization and degradation of cell corpses. Among them, TTR-52 and NRF-5 are bridging molecules that mediate recognition of cell corpses (Wang et al.,Nat Cell Biol2010; Zhang et al.,Curr Biol2012; Kang et al.,Genes Dev.2012). Myotubularin phosphatase MTM-1 coordinates with PI3 kinases PIKI-1 and VPS-34 to control initiation and completion of cell corpse engulfment (Zou et al.,PLos Genet2009; Cheng et al.,JCB2015, Liu et al.,JCB2018). Multiple Rab GTPases coordinate to regulate phagosome maturation and lysosomal degradation of apoptotic cells (Lu et al.,Development2008; Li et al.,Development2009; Guo et al.,PNAS2010, Yin et al.,JCB2017). Moreover, we found that non-apoptotic targets like residual bodies generated during spermatogenesis are recognized and cleared by the same molecular machinery that removes apoptotic cells (Huang et al.,Development2012). In addition, we demonstrate that the autophagy pathway contributes to cell corpse clearance through the PI3 kinase VPS-34(Cheng et al.,Autophagy2013). These findings have greatly advanced our understanding of how apoptotic cells are properly removed via the lysosome-dependent degradation pathways. Our current and planned research will focus on the regulatory machinery controlling cell corpse degradation. As evolutionarily conserved mechanisms are utilized to remove apoptotic cells, our studies inC. eleganswill deepen our understanding of this key process in both worms and mammals.