Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER–associated degradation (ERAD) is responsible for the clearance of misfolded pro–arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus. The results of this study demonstrate a role for ERAD in neuroendocrine cells and serve as a clinical example of the effect of misfolded ER proteins retrotranslocated through the membrane into the cytosol, where they are polyubiquitinated, extracted from the ER membrane, and degraded by the proteasome. Moreover, proAVP misfolding in hereditary central diabetes insipidus likely shares common physiopathological mechanisms with proinsulin misfolding in hereditary diabetes mellitus of youth.

抗利尿激素精氨酸加压素（AVP）的缺乏是尿崩症的基础，其特征是排泄了异常大量的稀尿和持续的口渴。在JCI的这一期中，Shi等人。报告说，与Sel1L-Hrd1 ER相关的降解（ERAD）负责清除ER中错误折叠的前精氨酸加压素（proAVP）。此外，Sel1L缺乏症的小鼠，无论是全局性的还是表达AVP的神经元内的特异性小鼠，都患有中枢性尿崩症。这项研究的结果证明了ERAD在神经内分泌细胞中的作用，并作为错误折叠的ER蛋白通过膜逆向转运到细胞质中的作用的临床实例，在那里它们被泛素化，从ER膜中提取并被蛋白酶体降解。 。而且，