Defective processing and trafficking of water channels in nephrogenic diabetes insipidus.
Nephrogenic diabetes insipidus (NDI) is a disease characterized by the inability of the kidney to concentrate urine upon stimulation with vasopressin. Mutations in the gene for aquaporin-2 (AQP2) are the cause of the autosomal recessive and autosomal dominant forms of NDI. Mutant AQP2 proteins, found in autosomal recessive NDI, were shown to be misfolded and retarded in the endoplasmic reticulum. One mutant protein leading to autosomal dominant NDI, E258K, has been analyzed in detail. It was shown that this mutant was not retarded in the endoplasmic reticulum but mainly retained in the Golgi network. Furthermore, this particular mutant was able to form heterotetramers with wild-type AQP2, in contrast to mutants found in autosomal recessive NDI. The subsequent misrouting of complexes containing wild-type and mutant AQP2 proteins explains dominant NDI.
Kamsteeg
E J
EJ
Department of Cell Physiology, University of Nijmegen, The Netherlands.
Deen
P M
PM
van Os
C H
CH
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics / Q000378:metabolism*; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation / Q000502:physiology; D011499:Protein Processing, Post-Translational
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins