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MIRAGE
Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI)
Summary
- Organism
- Homo sapiens (human)
- Reactome
- R-HSA-9036092
- PubChem
- R-HSA-9036092
- Description
-
- Arginine vasopressin (AVP(20-28)) is a 9 amino-acid long signal peptide produced by cleavage of the precursor protein AVP in the hypothalamus. It mediates the reabsorption of water in the kidney and its synthesis and release are physiologically regulated by plasma osmolarity, blood pressure and/or blood volume. AVP(20-28) binds to vasopressin receptors AVPR1 and 2, located on the basolateral surface of the kidney collecting duct. This binding results in interaction of AVPRs with the G protein alpha-s. Following a cascade of downstream events, ultimately the water channel aquaporin 2 (AQP2) translocates from intracellular stores to the apical surface where it functions as the entry site for water reabsorption. When water balance is achieved, plasma levels of AVP(20-28) drop and AQP2 levels in the apical plasma membrane are decreased.
Mutations in AVP make it unavailable to its AVPRs in the kidney, resulting in dysregulation of water reabsorption. This can cause familial neurohypophyseal diabetes insipidus (FNDI), an autosomal dominant disorder characterised by persistent excessive thirst resulting in constant drinking (polydipsia) and passage of large volumes of urine (polyuria). In FNDI, the production and release of AVP from the posterior pituitary gland is impaired (Moeller et al. 2013).
- Arginine vasopressin (AVP(20-28)) is a 9 amino-acid long signal peptide produced by cleavage of the precursor protein AVP in the hypothalamus. It mediates the reabsorption of water in the kidney and its synthesis and release are physiologically regulated by plasma osmolarity, blood pressure and/or blood volume. AVP(20-28) binds to vasopressin receptors AVPR1 and 2, located on the basolateral surface of the kidney collecting duct. This binding results in interaction of AVPRs with the G protein alpha-s. Following a cascade of downstream events, ultimately the water channel aquaporin 2 (AQP2) translocates from intracellular stores to the apical surface where it functions as the entry site for water reabsorption. When water balance is achieved, plasma levels of AVP(20-28) drop and AQP2 levels in the apical plasma membrane are decreased.
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
| UniProt ID | Protein Name | Gene Symbol | Pathway Viewer |
|---|---|---|---|
| P01185 | Vasopressin-neurophysin 2-copeptin |
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| P30518 | Vasopressin V2 receptor |
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