Rise and Fall, and Rise Again Phagosome Maturation Is Controlled by Two Kinases and One Phosphatase 英文参考文献.docVIP

Synopsis RiseandFall,andRiseAgain:PhagosomeMaturationIs ControlledbyTwoKinasesandOnePhosphatase RichardRobinson* FreelanceScienceWriter,Sherborn,Massachusetts,UnitedStatesofAmerica ‘‘Creative destruction’’ underlies not only dynamic economies, but also the development of multicellular organisms. Afterapoptosis,theprogrammedcelldeath that helps sculpt organs, dead cells are engulfedanddegraded,byeithersurround- ingcellsorspecializedphagocytes,suchas the macrophages of the mammalian im- munesystem. vivoinresponsetobothextracellularand intracellular stimuli, and the authors sus- pectedthattheworm’sonlyclassIIPI3- kinase,calledPIKI-1,mightbeproviding the residual signal. They showed that deletion of PIKI-1 also reduced the level of PtdIns(3)P, but again, not completely. Deletingthetwotogether,however,com- pletely abolished PtdIns(3)P on phagoso- Apoptoticcellsareengulfedintoamem- brane-bound organelle called a phago- some. Engulfment triggers the production ofasignalingmoleculeonthephagosome surface,calledphosphatidylinositol3-phos- phate, or PtdIns(3)P. This molecule then attracts a suiteof proteinsthat help bring digestiveorganelles,suchaslysosomesand endosomes, to phagosomes in order to completethedegradationofthedeadcell. For reasons still unknown, the initial wave of PtdIns(3)P subsides after about 15minutes,tobefollowedabout10min- uteslaterbyasecond,smallerwave.While thewhyremainsobscure,thehowisnow much clearer, thanks to detailed work by Nan Lu, Zheng Zhou, and colleagues, whoshowthatinCaenorhabditiselegans ,the PtdIns(3)Poscillationisduetothecoordi- nated efforts of two kinases, which create thesignalingmolecule,andonephospha- tase, whichdestroys it.The authors show that the tight coupling of their opposed actionsisrequiredforsuccessfuldegrada- tionoftheengulfedcell. mal surfaces, and halted phagosome maturation entirely. Without PtdIns(3)P, The precise temporal control of phagosomes did not accumulate one PtdIns(3)P (illustrated as flames) pro- duc