RGD Reference Report - Heterologous expression of human vasopressin-neurophysin precursors in a pituitary cell line: defective transport of a mutant protein from patients with familial diabetes insipidus.

General

Heterologous expression of human vasopressin-neurophysin precursors in a pituitary cell line: defective transport of a mutant protein from patients with familial diabetes insipidus.
Authors:	Olias, G Richter, D Schmale, H
Citation:	Olias G, etal., DNA Cell Biol 1996 Nov;15(11):929-35.
RGD ID:	734624
Pubmed:	PMID:8945633 (View Abstract at PubMed)
DOI:	DOI:10.1089/dna.1996.15.929 (Journal Full-text)
Familial hypothalamic diabetes insipidus is an autosomal dominant disorder characterized by deficient vasopressin synthesis. Different point mutations in the vasopressin-neurophysin (VP-NP) precursor gene have been found in affected families. In a Dutch kindred, a single G to T transversion in the NP-encoding exon B of one allele converts the highly conserved glycine 17 to a valine residue. In order to examine whether this point mutation affects the processing and transport of the VP-NP precursor, the normal (HV2) and mutant (MT6) vasopressin cDNAs were stably expressed in the mouse pituitary cell line AtT20. The normal precursor was correctly glycosylated and processed, and NP was detected in the culture medium. Secretion of NP was stimulated by 8-bromo-cAMP, indicating that the normal precursor was targeted to the regulated secretory pathway. In contrast, the mutant precursor was synthesized, but processing and secretion were dramatically reduced. The mutant precursor was core-glycosylated but remained endoglycosidase H-sensitive, suggesting that the protein did not reach the trans-Golgi network. These results were supported by immunocytochemical studies. In HV2 cells, NP derived from the precursor was concentrated in the tips of the cell processes where secretory granules accumulate. In MT6 cells, NP staining was restricted to the endoplasmic reticulum (ER) as determined by colocalization with an ER-resident protein, BiP. These results suggest that the mutation within the conserved part of NP alters the conformation of the precursor and thus triggers its retention in the ER.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
diabetes insipidus		IAGP		734624		RGD
diabetes insipidus		ISO	AVP (Homo sapiens)	734624; 734624		RGD

Objects Annotated

Genes (Rattus norvegicus)

Avp (arginine vasopressin)

Genes (Mus musculus)

Avp (arginine vasopressin)

Genes (Homo sapiens)

AVP (arginine vasopressin)

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Heterologous expression of human vasopressin-neurophysin precursors in a pituitary cell line: defective transport of a mutant protein from patients with familial diabetes insipidus.