Center of Translational Medicine, Central Hospital of Zibo, Shandong University, Zibo, China.
Clin Genet. 2018 Jan;93(1):178-181. doi: 10.1111/cge.13081. Epub 2017 Oct 29.
Mutations in Plastin-3 (PLS3) have been identified as a cause of X-linked osteoporosis. To reveal the molecular mechanism of PLS3 on osteoporosis, we characterized the p.Ala253_Leu254insAsn mutation in PLS3. We first identified Lymphocyte cytosolic protein 1 (LCP1) as a binding partner of PLS3 and the mutation disrupted the interaction between them. We then confirmed the roles of PLS3 and LCP1 in the regulation of intracellular Ca , which was weakened by the mutant PLS3. Moreover, the interaction between PLS3 and LCP1 was enhanced under a low concentration of extracellular Ca . However, the mutation in PLS3 weakened the responsiveness. The reduced regulation on Ca caused by p.Ala253_Leu254insAsn may be the possible molecular mechanism of osteoporosis.
PLS3 基因突变已被确定为 X 连锁骨质疏松症的病因。为了揭示 PLS3 导致骨质疏松症的分子机制，我们对 PLS3 中的 p.Ala253_Leu254insAsn 突变进行了特征分析。我们首先鉴定了淋巴细胞胞浆蛋白 1（LCP1）是 PLS3 的结合伴侣，该突变破坏了它们之间的相互作用。然后，我们证实了 PLS3 和 LCP1 在细胞内 Ca 调节中的作用，突变型 PLS3 削弱了这一作用。此外，在低浓度细胞外 Ca 下，PLS3 和 LCP1 之间的相互作用增强。然而，PLS3 中的突变削弱了这种反应能力。p.Ala253_Leu254insAsn 引起的 Ca 调节减少可能是骨质疏松症的潜在分子机制。
