Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Shared Equipment Authority, Rice University, Houston, Texas, USA.
Dev Dyn. 2022 Jul;251(7):1209-1222. doi: 10.1002/dvdy.461. Epub 2022 Feb 18.
Absence of Golgi microtubule-associated protein 210 (GMAP210), encoded by the TRIP11 gene, results in achondrogenesis. Although TRIP11 is thought to be specifically required for chondrogenesis, human fetuses with the mutation of TRIP11 also display bony skull defects where chondrocytes are usually not present. This raises an important question of how TRIP11 functions in bony skull development.
We disrupted Trip11 in neural crest-derived cell populations, which are critical for developing skull in mice. In Trip11 mutant skulls, expression levels of ER stress markers were increased compared to controls. Morphological analysis of electron microscopy data revealed swollen ER in Trip11 mutant skulls. Unexpectedly, we also found that Golgi stress increased in Trip11 mutant skulls, suggesting that both ER and Golgi stress-induced cell death may lead to osteopenia-like phenotypes in Trip11 mutant skulls. These data suggest that Trip11 plays pivotal roles in the regulation of ER and Golgi stress, which are critical for osteogenic cell survival.
We have recently reported that the molecular complex of ciliary protein and GMAP210 is required for collagen trafficking. In this paper, we further characterized the important role of Trip11 being possibly involved in the regulation of ER and Golgi stress during skull development.
由 TRIP11 基因编码的高尔基微管相关蛋白 210（GMAP210）的缺失导致软骨发育不全。尽管 TRIP11 被认为是软骨生成所必需的，但具有 TRIP11 突变的人类胎儿也显示出通常不存在软骨细胞的骨颅骨缺陷。这就提出了一个重要的问题，即 TRIP11 如何在骨颅骨发育中发挥作用。
我们破坏了神经嵴来源细胞群体中的 Trip11，这些细胞对于小鼠颅骨的发育至关重要。在 Trip11 突变的颅骨中，与对照组相比，内质网应激标志物的表达水平增加。电镜数据的形态分析显示 Trip11 突变的颅骨中内质网肿胀。出乎意料的是，我们还发现 Golgi 应激在 Trip11 突变的颅骨中增加，这表明内质网和 Golgi 应激诱导的细胞死亡可能导致 Trip11 突变的颅骨出现类骨质疏松表型。这些数据表明，Trip11 在调节内质网和 Golgi 应激中发挥关键作用，这对于成骨细胞的存活至关重要。
我们最近报道了纤毛蛋白和 GMAP210 的分子复合物对于胶原运输是必需的。在本文中，我们进一步表征了 Trip11 可能参与调节颅骨发育过程中内质网和 Golgi 应激的重要作用。
