简介：Directionalmigrationofleukocytesisindispensabletoinnateimmunityforhostdefense.However,recruitmentofleukocytestoasiteoftissueinjuryalsoconstitutesaleadingcauseforinflammatoryresponses.Mechanistically,itinvolvesacascadeofcellulareventspreciselyregulatedbytemporalandspatialpresentationofarepertoireofmoleculesinthemigratingleukocytesandtheirsurroundings(microenvironments).HereIwillsummarizetheemergingevidencethathasshedlightsontheunderlyingmolecularmechanismfordirectionalmigrationofleukocytes,whichhasguidedthetherapeuticaldevelopmentforinnovativeanti-inflammatorymedicines.

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简介：Twomajorapoptosispathwayshavebeendefinedinmammaliancells,theFas/TNF-R1deathreceptorpathwayandthemitochondriapathway.TheBcl-2familyproteinsconsistofbothanti-apoptosisandpro-apoptosismembersthatregulateapoptosis,mainlybycontrollingthereleaseofcytochromecandothermitochondrialapoptoticevents.However,deathsignalsmediatedbyFas/TNF-R1receptorscanusuallyactivatecaspasesdirectly,bypassingtheneedformitochondriaandescapingtheregulationbyBcl-2familyproteins.Bidisanovelpro-apoptosisBcl-2familyproteinthatisactivatedbycaspase8inresponsetoFas/TNF-R1deathreceptorsignals.ActivatedBidistranslocatedtomitochondriaandinducescytochromecrelease,whichinturnactivatesdownstreamcaspases.Suchaconnectionbetweenthetwoapoptosispathwayscouldbeimportantforinductionofapoptosisincertaintypesofcellsandresponsibleforthepathogenesisofanumberofhumandiseases.

简介：新鲜的水息肉水螅属于门Cnidaria，它在bilaterians的外观前从后生动物的系分叉。以便在metazoans理解apoptosis的进化，我们开始阐明了在这个模型有机体的分子的细胞死亡机械。基于EST和整个水螅染色体集会，我们识别了15caspases。我们证明一个人在apoptosis期间被激活，四与N终端DED，卡片或DD领域有开始者caspases的特征，二在vitro经历autoprocessing。另外，我们描述七Bcl-2-like和二象Bak一样蛋白质。为大多数Bcl-2家庭蛋白质，我们观察了mitochondrial本地化。当在哺乳动物的房间表示了时，象HyBak一样1和2强烈导致的apoptosis。禁止的apoptosis与显示出特别强壮的保护的效果的HyBcl-2-like4在哺乳动物的房间由camptothecin劝诱了的六个Bcl-2家庭成员。这蛋白质也与象HyBak一样交往了1在酵母二混血儿的试金。在它的BH3领域的保存白氨酸的变化两个都与象HyBak一样废除了相互作用1并且anti-apoptotic效果。而且，我们BH-3-only描述新奇水螅蛋白质。这些之一与Bcl-2-like4交往了并且在哺乳动物的房间导致了apoptosis。我们的数据显示为房间死亡规定的一个复杂网络的进化在多细胞的组织的最早、最简单的水平产生了，它在此展出了一复杂性实质地高级比在protostome模型有机体Caenorhabditis和果蝇。