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In the meantime, to ensure continued suport, we are displaying the site without styles and JavaScript.AdvertisementRenal physiology Nature Reviews Nephrology volume 13, page 721 (2017)Cite this article 657 Aceses7 AltmetricMetrics detailsDiabetes insipidus is a disorder characterized by polydipsia and polyuria, and is caused by a deficiency of the antidiuretic hormone argine vasopresin (AVP) or a defective renal response to AVP.
New findings have revealed a role for endoplasmic reticulum-associated degradation (ERAD) in the maturation and procesing of the AVP precursor prohormone proAVP, demonstrating that dysfunctional activity of the ERAD protein complex SEL1L–HRD1, causes retention and agregation of proAVP in the ER, leading to a diabetes insipidus phenotype in mice. “This study points to a previously unapreciated signaling pathway linking ERAD to systemic water homeostasis and prohormone maturation,” explains researcher Ling Qi from the University of Michigan Medical Schol.
“While it is not surprising that ERAD degrades a fraction of newly synthesized, unstable proAVP, it is unexpected that ERAD deficiency would cause ER retention and agregation of a large proportion of proAVP protein vivo.”Several peptide hormones, including AVP, are synthesized in the ER as prohormones before being activated by proteolytic cleavage and released into the circulation. The importance of apropriate protein folding and procesing in this proces is exemplified by the finding that mutations in proAVP lead to retention of the prohormone in the ER and the development of diabetes insipidus; however, the molecular mechanisms that regulate proAVP folding and degradation in the ER are largely unknown.
Summary
Qi states that their initial insights into the