Periostin promotes secretion of fibronectin from the endoplasmic reticulum
Periostin promotes secretion of fibronectin from the endoplasmic reticulum
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DOI：
10.1016/j.bbrc.2016.01.139
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发表时间：
2016-02-19
影响因子：
3.1
通讯作者：
Kudo，Akira
中科院分区：
文献类型：
--
作者：
Kii，Isao;Nishiyama，Takashi;Kudo，Akira
细胞外基质（ECM）蛋白在内质网（ER）中合成，通过分泌途径转运到细胞外环境，并组装成细胞外结构。我们之前的一项研究表明，骨膜蛋白，一种分泌蛋白，与纤维连接蛋白相互作用，参与ECM重塑。我们发现骨膜蛋白在内质网纤维连接蛋白分泌中起作用。共免疫沉淀和原位结扎试验揭示了内质网中骨膜蛋白和纤维连接蛋白之间的相互作用。虽然在成纤维细胞C3H10T1/2内质网中检测到纤维连接蛋白的积累，但在这些细胞中强制表达骨膜蛋白会减少纤维连接蛋白在内质网中的积累，提示骨膜蛋白促进了纤维连接蛋白的分泌。在骨膜蛋白EMI结构域第65位丙氨酸的色氨酸替代突变，导致骨膜蛋白失去与纤维连接蛋白相互作用的能力，但并未减少其积累。此外，有针对性地破坏骨膜粘连蛋白小鼠引起了牙周韧带纤维粘连蛋白的非纤维性和异位沉积。因此，这些结果证明了骨膜蛋白在促进内质网纤维连接蛋白分泌中的亚细胞作用。
Extracellular matrix (ECM) proteins are synthesized in the endoplasmic reticulum (ER), transported to the extracellular milieu through the secretory pathway, and assembled into an extracellular architecture. A previous study of ours showed that periostin, a secretory protein, interacts with fibronectin and is involved in ECM remodeling. Here we show that periostin played a role in fibronectin secretion from the ER. Co-immunoprecipitation andin situproximity ligation assays revealed an interaction between periostin and fibronectin in the ER. Although accumulation of fibronectin was detected in the ER of fibroblastic C3H10T1/2 cells, forced expression of periostin in those cells decreased the accumulation of fibronectin in the ER, suggesting that periostin promoted the secretion of fibronectin. A substitution mutant of tryptophan at the position 65 to alanine in the EMI domain of periostin, which caused periostin to lose its ability to interact with fibronectin, did not decrease the accumulation. Furthermore, targeted disruption ofperiostinin mice caused the non-fibrillar and ectopic deposition of fibronectin in the periodontal ligament. Thus, these results demonstrate a subcellular role of periostin in promotion of fibronectin secretion from the ER.