Dominant pro-vasopressin mutants that cause diabetes insipidus form disulfide-linked fibrillar aggregates in the endoplasmic reticulum
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منابع مشابه
Mutations in the vasopressin prohormone involved in diabetes insipidus impair endoplasmic reticulum export but not sorting.
Familial neurohypophysial diabetes insipidus is characterized by vasopressin deficiency caused by heterozygous expression of a mutated vasopressin prohormone gene. To elucidate the mechanism of this disease, we stably expressed five vasopressin prohormones with a mutation in the neurophysin moiety (NP14G-->R, NP47E-->G, NP47DeltaE, NP57G-->S, and NP65G-->V) in the neuroendocrine cell lines Neur...
متن کاملDegradation of wild-type vasopressin precursor and pathogenic mutants by the proteasome.
Mutations in the gene encoding the antidiuretic hormone arginine vasopressin cause autosomal dominant neurogenic diabetes insipidus. Autoptic data in affected individuals suggest that the neurons expressing mutant vasopressin undergo selective degeneration. Expression studies have shown that the mutants are retained in the endoplasmic reticulum, but how this trafficking defect is linked to neur...
متن کاملMolecular basis of autosomal dominant neurohypophyseal diabetes insipidus. Cellular toxicity caused by the accumulation of mutant vasopressin precursors within the endoplasmic reticulum.
Mutations in the arginine vasopressin (AVP) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus (FNDI). The dominant inheritance pattern has been postulated to reflect neuronal toxicity of the mutant proteins, but the mechanism for such cytotoxicity is unknown. In this study, wild-type or several different mutant AVP genes were stably expressed in neuro2A neuroblastoma ce...
متن کاملEndoplasmic reticulum derangement in hypothalamic neurons of rats expressing a familial neurohypophyseal diabetes insipidus mutant vasopressin transgene.
Human familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant endocrine disorder that presents in early childhood as excessive drinking and urination as a consequence of a progressive loss of secretion of vasopressin (VP) from posterior pituitary nerve terminals. Mutations in the VP gene have been implicated as the cause of FNDI, but the mechanisms by which these mutants ma...
متن کاملFHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation.
FHL1 mutations cause several clinically heterogeneous myopathies, including reducing body myopathy (RBM), scapuloperoneal myopathy (SPM) and X-linked myopathy with postural muscle atrophy (XMPMA). The molecular mechanisms underlying the pathogenesis of FHL1 myopathies are unknown. Protein aggregates, designated 'reducing bodies', that contain mutant FHL1 are detected in RBM muscle but not in se...
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ژورنال
عنوان ژورنال: Journal of Cell Science
سال: 2009
ISSN: 1477-9137,0021-9533
DOI: 10.1242/jcs.051136