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The molecular structure and function of sorting nexin 10 in skeletal disorders, cancers, and other pathological conditions
Author(s) -
Xu Jiake,
Qiu Heng,
Zhao Jinmin,
Pavlos Nathan J.
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30173
Subject(s) - sorting nexin , microbiology and biotechnology , endosome , osteopetrosis , biology , bone resorption , bone marrow , cancer research , immunology , endocrinology , intracellular
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.