Distinct PAR/IQGAP expression patterns during murine development: implications for thrombin-associated cytoskeletal reorganization
Distinct PAR/IQGAP expression patterns during murine development: implications for thrombin-associated cytoskeletal reorganization
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DOI：
10.1007/s00335-004-2370-8
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发表时间：
2004-08-01
期刊：
影响因子：
2.5
通讯作者：
Bahou, WF
中科院分区：
文献类型：
--
作者：
Cupit, LD;Schmidt, VA;Bahou, WF
凝血酶在许多成体和胚胎细胞过程中起关键作用，通过两种高亲和力凝血酶受体系统发挥其作用：蛋白酶激活受体1（PAR 1）和PAR 3/PAR 4系统。hPAR 1和hPAR 3在人类基因组中共聚，hPAR 3包含在hIQGAP 2中，hIQGAP 2是一种推定的GT3活化蛋白，具有与细胞骨架重组相关的肌动蛋白聚合功能。由于hPAR与hIQGAP 2在人类基因组中共定位，并在血小板凝血酶信号传导途径中与该蛋白协同发挥作用，因此我们进一步表征了这些基因在发育中的胚胎和成人组织中的特征。我们证实了小鼠13号染色体上存在mIQGAP 2/mPAR基因簇，并显示其组织与人类相似，只是小鼠PAR 3被翻译出正向（有义）链。北方分析表明，有限的mPAR 3表达在成人组织中，虽然它的表达在胚胎发育过程中是明显的在E15的软骨，脑，角质形成细胞。m1 QGAP 1和m1 QGAP 2在研究的15个成人组织中的11个中具有一致的表达模式。相比之下，整个胚胎表现出主要的mIQGAP 1表达开始于E7和E17明显。整个胚胎（E9-EI 6）的原位杂交显示了不同的组织依赖性mIQGAP 1/mIQGAP 2表达模式。在研究的大多数（12/15）成人组织中观察到mPAR 1与mIQGAP 1或mIQGAP 2的一致表达（不存在或存在）。类似地，在不存在mIQGAP 1或mIQGAP 2的情况下，在胚胎发生期间没有mPAR 3表达的证据。这些数据提供了一个全景调查PAR/IQGAP表达作为一个初步的方法来解剖凝血酶信号通路与细胞骨架重组。
Thrombin has a critical role in many adult and embryologic cellular processes, exerting its effects through two high-affinity thrombin receptor systems: protease-activated receptor 1 (PAR1) and the PAR3/PAR4 system. Both hPAR1 and hPAR3 are coclustered in the human genome, with hPAR3 encompassed within hIQGAP2, a putative GTPase activating protein with actin polymerizing functions linked to cytoskeletal reorganization. Since hPARs colocalize with hIQGAP2 in the human genome and function coordinately with this protein in platelet thrombin signaling pathways, we have further characterized these genes in developing embryonic and adult tissues. We confirmed the presence of a mIQGAP2/mPAR gene cluster on murine Chromosome 13 and showed it to be organized similarly to that in humans, except that murine PAR3 is translated off the forward (sense) strand. Northern analysis demonstrated limited mPAR3 expression in adult tissues, although its expression during embryogenesis was evident at E15 in cartilage, brain, and keratinocytes. m1QGAPs 1 and 2 had congruent expression patterns in 11 of 15 adult tissues studied. In contrast, whole embryos demonstrated predominant mIQGAP1 expression starting at E7 and evident to E17. In situ hybridization of whole embryos (E9-EI6) demonstrated distinct patterns of tissue-dependent mIQGAP1/mIQGAP2 expression. Concordant expression (absence or presence) of mPAR1 with either mIQGAP1 or mIQGAP2 was seen in the majority (12 of 15) of adult tissues studied. Similarly, there was no evidence for mPAR3 expression during embryogenesis in the absence of either mIQGAP1 or mIQGAP2. These data provide a panoramic survey of PAR/IQGAP expression as an initial approach to dissect thrombin signaling pathways linked to cytoskeletal reorganization.