Author:
Xu Cheng,Wei Zhixin,Lv Longfei,Dong Xiaoyu,Xia Wenwen,Xing Junqiao,Liu Hongni,Zhao Xue,Liu Yuan,Wang Weihua,Jiang Haochen,Gong Yeli,Liu Cong,Xu Kai,Wang Siyuan,Akimoto Yoshie,Hu Zhangfeng
Abstract
ABSTRACTCompartmentation via filamentation is an evolutionarily conserved subcellular structure that fine-tunes the inherent activity of proteins. Cytoophidia represent a typical class of filamentous structures controlling enzymatic activities. Despite eukaryotic cells containing both cytoplasmic cytoophidia and nuclear cytoophidia, the physiological significance of nuclear cytoophidia is largely unknown. Here we show that nuclear filamentation inhibits the transcriptional activity of Impdh2 required for limb formation and bone resorption. Impdh2 deletion in mouse limb mesenchymal progenitors causes severe skeletal dysplasia by impairing endochondral ossification and chondrocyte differentiation. Additionally, Impdh2 deficiency in myeloid lineages leads to an increased bone mass via impeding osteoclast differentiation. Furthermore, Impdh2 regulates osteoclastic mitochondrial biogenesis and function. We propose that the nuclear compartmentalization of Impdh2 regulates the transcriptional activity during skeletal development and homeostasis.
Publisher
Cold Spring Harbor Laboratory