The Caenorhabditis elegans ERp60 homolog protein disulfide isomerase-3 has disulfide isomerase and transglutaminase-like cross-linking activity and is involved in the maintenance of body morphology
The Caenorhabditis elegans ERp60 homolog protein disulfide isomerase-3 has disulfide isomerase and transglutaminase-like cross-linking activity and is involved in the maintenance of body morphology
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DOI：
10.1074/jbc.m210510200
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发表时间：
2003-02-07
影响因子：
4.8
通讯作者：
Page, AP
中科院分区：
文献类型：
--
作者：
Eschenlauer, SCP;Page, AP
从秀丽隐杆线虫中分离到一个新的蛋白质二硫键异构酶基因pdi-3。该基因编码一种与ERp 60类硫氧还蛋白蛋白相关的酶，并被发现表现出不寻常的酶性质。重组蛋白显示二硫键异构酶活性和钙依赖性转氨酶样交联活性。pdi-3转录本在发育过程中组成型表达，编码的蛋白质存在于许多组织中，包括肠道和皮下组织。线虫皮下组织合成称为角质层的必需胶原性细胞外基质（ECM）。通过双链RNA干扰的转录破坏在几个C.具有减弱的cu的线虫突变等位基因：sqt-3（e2117），dpy-18（e364，ok 162和bx 26）。这些线虫表现出严重的矮胖表型和破坏侧翼，不稳定的角质层和异常的男性和雌雄同体的尾巴形态。这些缺陷被证实与皮下接缝细胞异常一致，并与角质层胶原蛋白的严重破坏相对应。野生型线虫没有表现出可观察到的形态学缺陷;然而，表皮胶原蛋白定位在pdi-3 RNA干扰后被轻度破坏。因此，不寻常的硫氧还蛋白酶，蛋白质二硫键异构酶-3，可能在ECM组装中发挥作用。这种酶是必要的适当维护胚后的身体形状的菌株与削弱角质层，可能通过ECM稳定通过交联活性，二硫键异构酶蛋白折叠活性，蛋白质二硫键异构酶伴侣活性，或通过多功能事件。
A novel protein disulfide isomerase gene, pdi-3, was isolated from the nematode Caenorhabditis elegans. This gene encodes an enzyme related to the ERp60 class of thioredoxin proteins and was found to exhibit unusual enzymatic properties. Recombinant protein displayed both disulfide bond isomerase activity and calcium-dependent transglutaminase-like cross-linking activity. The pdi-3 transcript was developmentally constitutively expressed, and the encoded protein is present in many tissues including the gut and the hypodermis. The nematode hypodermis synthesizes the essential collagenous extracellular matrix (ECM) called the cuticle. Transcript disruption via double-stranded RNA interference resulted in dramatic and specific synthetic phenotypes in several C. elegans mutant alleles with weakened cuticles: sqt-3(e2117), dpy-18(e364, ok162, and bx26). These nematodes displayed severe dumpy phenotypes and disrupted lateral alae, a destabilized cuticle and abnormal male and hermaphrodite tail morphologies. These defects were confirmed to be consistent with hypodermal seam cell abnormalities and corresponded with the severe disruption of a cuticle collagen. Wild type nematodes did not exhibit observable morphological defects; however, cuticle collagen localization was mildly disrupted following pdi-3 RNA interference. The unusual thioredoxin enzyme, protein disulfide isomerase-3, may therefore play a role in ECM assembly. This enzyme is required for the proper maintenance of postembryonic body shape in strains with a weakened cuticle, perhaps through ECM stabilization via cross-linking activity, disulfide isomerase protein folding activity, protein disulfide isomerase-chaperone activity, or via multifunctional events.