Birsoy Bilge, Berg Linnea, Williams P Huw, Smith James C, Wylie Christopher C, Christian Jan L, Heasman Janet
Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Development. 2005 Feb;132(3):591-602. doi: 10.1242/dev.01599. Epub 2005 Jan 5.
XPACE4 is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the TGFbeta family of signaling molecules. Studies in mouse suggest it may have important roles in regulating embryonic tissue specification. Here, we examine the role of XPACE4 in Xenopus development and make three novel observations: first, XPACE4 is stored as maternal mRNA localized to the mitochondrial cloud and vegetal hemisphere of the oocyte; second, it is required for the endogenous mesoderm inducing activity of vegetal cells before gastrulation; and third, it has substrate-specific activity, cleaving Xnr1, Xnr2, Xnr3 and Vg1, but not Xnr5, Derriere or ActivinB pro-proteins. We conclude that maternal XPACE4 plays an important role in embryonic patterning by regulating the production of a subset of active mature TGFbeta proteins in specific sites.
XPACE4是枯草杆菌蛋白酶/克新蛋白家族中前体蛋白转化酶的一员。它能切割许多前体蛋白以释放其活性蛋白，包括转化生长因子β（TGFβ）信号分子家族的成员。对小鼠的研究表明，它可能在调节胚胎组织特化中发挥重要作用。在此，我们研究了XPACE4在非洲爪蟾发育中的作用，并得出三个新的发现：第一，XPACE4以母源mRNA的形式储存，定位于卵母细胞的线粒体云团和植物半球；第二，在原肠胚形成前，它是植物细胞内源性中胚层诱导活性所必需的；第三，它具有底物特异性活性，能切割Xnr1、Xnr2、Xnr3和Vg1，但不能切割Xnr5、Derriere或激活素B前体蛋白。我们得出结论，母源XPACE4通过调节特定部位活性成熟TGFβ蛋白子集的产生，在胚胎模式形成中发挥重要作用。
