Michigami Toshimi
Disorders Caused by Mutations in Calcium-Sensing Receptor and Related Diseases.
Clin Calcium. 2017;27(4):521-527.
Sensing of extracellular calcium(Ca2+)levels involves the Ca-sensing receptor(CaSR), its downstream signaling molecule Gα11, and the adaptor-related protein complex 2(AP2)that plays a role in clathrin-dependent endocytosis of CaSR. Inactivating mutations in CaSR cause familial hypocalciuric hypercalcemia type 1(FHH1)and neonatal severe hyperparathyroidism(NSHPT), while activating mutations lead to autosomal dominant hypocalcemia type 1(ADH1)and Bartter syndrome type Ⅴ. Recent studies have identified that inactivating mutations in Gα11 and σ-subunit of AP2(AP2σ)also cause FHH, and these conditions have been classified as FHH2 and FHH3, respectively. In addition, it has been revealed that activating mutations in Gα11 are responsible for ADH(ADH2). Calcimimetics and calcilytics may be beneficial in the treatment of these disorders.
细胞外钙（Ca2+）水平的感知涉及钙敏感受体（CaSR）、其下游信号分子Gα11以及在CaSR网格蛋白依赖性内吞作用中发挥作用的衔接蛋白相关蛋白复合物2（AP2）。CaSR的失活突变会导致1型家族性低钙血症高钙血症（FHH1）和新生儿重症甲状旁腺功能亢进症（NSHPT），而激活突变则会导致1型常染色体显性低钙血症（ADH1）和Ⅴ型巴特综合征。最近的研究发现，Gα11和AP2的σ亚基（AP2σ）的失活突变也会导致FHH，这些病症分别被归类为FHH2和FHH3。此外，研究表明Gα11的激活突变是导致ADH（ADH2）的原因。拟钙剂和促钙剂可能对这些疾病的治疗有益。
