Abl Is Able to Inhibit Cell Engulfment 英文参考文献.docVIP

Abl Is Able to Inhibit Cell Engulfment Richard Robinson | doi:10.1371/journal.pbio.1000104 Programmed cell death is essential to development—it’s how the tiny mitten of a growing hand becomes a glove of individuated fingers, for instance. To dispose of all those cellular corpses, nearby cells (or roving specialists such as the immune system’s macrophages) engulf their dead neighbors and digest the remains. Engulfment, therefore, is a valuable process, and it is known to be promoted by two parallel signaling pathways. But preventing engulfment is also important (one can almost hear a little cell’s faint cry, “I’m not dead yet!”); however, little is known about how the process is inhibited. In a new study, Michael Hurwitz and colleagues describe a pathway that does just that. To wrap itself around another cell, the engulfing cell must recruit new a membrane and completely reorganize its cytoskeleton, and these processes are regulated by the two pro-engulfment pathways, known as the CED-1 pathway (thought to be responsible primarily for membrane recruitment) and the CED-10 Rac pathway (thought to be responsible primarily for cytoskeletal rearrangement). doi:10.1371/journal.pbio.1000104.g001 For many years, two molecular pathways were known to regulate the engulfment of apoptotic cells. Now, a third pathway has been identified in C. elegans that is inhibited by the Abl tyrosine kinase oncoprotein. Cytoskeletal remodeling is also developing larvae, they ruled out this and other alternatives, leading them to conclude that ABL-1 directly inhibited engulfment. The protein appears to exert its effect on the engulfing cell, because it inhibited engulfment when it was expressed everywhere except the engulfed cell. The authors then explored the function of a known interactor with ABL-1, called ABI-1. In contrast to mutant ABL-1, mutations in ABI-1 reduced engulfment, just as mutations in the two previously known pro- engulfment pathways did. And it did so whether or not ABL