纤毛和高尔基体蛋白的分子复合物对于颅骨发育至关重要。
The molecular complex of ciliary and golgin protein is crucial for skull development.
机构信息
Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Shared Equipment Authority, Rice University, Houston, TX 77005, USA.
出版信息
Development. 2021 Jul 1;148(13). doi: 10.1242/dev.199559.
Intramembranous ossification, which consists of direct conversion of mesenchymal cells to osteoblasts, is a characteristic process in skull development. One crucial role of these osteoblasts is to secrete collagen-containing bone matrix. However, it remains unclear how the dynamics of collagen trafficking is regulated during skull development. Here, we reveal the regulatory mechanisms of ciliary and golgin proteins required for intramembranous ossification. During normal skull formation, osteoblasts residing on the osteogenic front actively secreted collagen. Mass spectrometry and proteomic analysis determined endogenous binding between ciliary protein IFT20 and golgin protein GMAP210 in these osteoblasts. As seen in Ift20 mutant mice, disruption of neural crest-specific GMAP210 in mice caused osteopenia-like phenotypes due to dysfunctional collagen trafficking. Mice lacking both IFT20 and GMAP210 displayed more severe skull defects compared with either IFT20 or GMAP210 mutants. These results demonstrate that the molecular complex of IFT20 and GMAP210 is essential for the intramembranous ossification during skull development.
膜内成骨，即间充质细胞直接转化为成骨细胞，是颅骨发育的一个特征过程。这些成骨细胞的一个关键作用是分泌含有胶原蛋白的骨基质。然而，胶原蛋白运输的动力学如何在颅骨发育过程中被调节仍不清楚。在这里，我们揭示了膜内成骨所必需的纤毛和高尔基体蛋白的调节机制。在正常颅骨形成过程中，位于成骨前缘的成骨细胞积极分泌胶原蛋白。质谱和蛋白质组学分析确定了内源性纤毛蛋白 IFT20 与高尔基体蛋白 GMAP210 之间的结合。正如在 Ift20 突变小鼠中所见，破坏神经嵴特异性 GMAP210 会导致胶原运输功能障碍，从而引起类骨质疏松表型。与 IFT20 或 GMAP210 突变体相比，缺乏 IFT20 和 GMAP210 的小鼠表现出更严重的颅骨缺陷。这些结果表明，IFT20 和 GMAP210 的分子复合物对于颅骨发育过程中的膜内成骨是必不可少的。
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