The molecular structure and function of sorting nexin 10 in skeletal disorders, cancers, and other pathological conditions,Journal of Cellular Physiology

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The molecular structure and function of sorting nexin 10 in skeletal disorders, cancers, and other pathological conditions
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-11-25 , DOI: 10.1002/jcp.30173
Jiake Xu ₁ , Heng Qiu ₁ , Jinmin Zhao ₂ , Nathan J Pavlos ₁

Affiliation

SNX10 is a member of the phox homology domain‐containing family of phosphoinositide‐binding proteins. Intracellularly, SNX10 localizes to endosomes where it mediates intracellular trafficking, endosome organization, and protein localization to the centrosome and cilium. It is highly expressed in bone and the gut where it participates in bone mineral and calcium homeostasis through the regulation of osteoclastic bone resorption and gastric acid secretion, respectively. Not surprisingly, patients harboring mutations in SNX10 mutation manifest a phenotype of autosomal recessive osteopetrosis or malignant infantile osteopetrosis, which is clinically characterized by dense bones with increased cortical bone into the medullary space with bone marrow occlusion or depletion, bone marrow failure, and anemia. Accordingly, SNX10 mutant osteoclasts exhibit impaired bone resorptive capacity. Beyond the skeleton, there is emerging evidence implicating SNX10 in cancer development, metabolic disorders, inflammation, and chaperone‐mediated autophagy. Understanding the structural basis through which SNX10 exerts its diverse biological functions in both cell and tissue‐specific manners may therefore inform new therapeutic opportunities toward the treatment and management of SNX10‐related diseases.

中文翻译：

在骨骼疾病、癌症和其他病理状况中分选 nexin 10 的分子结构和功能

SNX10 是含有 phox 同源结构域的磷酸肌醇结合蛋白家族的成员。在细胞内，SNX10 定位于内体，在那里它介导细胞内运输、内体组织和蛋白质定位到中心体和纤毛。它在骨骼和肠道中高度表达，分别通过调节破骨细胞的骨吸收和胃酸分泌参与骨矿物质和钙稳态。毫不奇怪，携带 SNX10 突变的患者表现出常染色体隐性骨硬化症或恶性婴儿骨硬化症的表型，其临床特征是致密骨，皮质骨进入髓腔，骨髓闭塞或耗竭，骨髓衰竭和贫血。因此，SNX10 突变的破骨细胞表现出骨吸收能力受损。除了骨骼之外，还有新的证据表明 SNX10 与癌症发展、代谢紊乱、炎症和分子伴侣介导的自噬有关。因此，了解 SNX10 以细胞和组织特异性方式发挥其多种生物学功能的结构基础可能为治疗和管理 SNX10 相关疾病提供新的治疗机会。

更新日期：2020-11-25

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