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A diabetes insipidus vasopressin prohormone altered outside the central core of neurophysin accumulates in the endoplasmic reticulum.

Abstract：

:Over 20 mutations affecting the neurophysin moiety of the vasopressin prohormone, have been identified in families suffering from familial neurohypophysial diabetes insipidus (FNDI). Only one of these, NP87E-->stop, is located outside the central conserved domain implicated in sorting of the vasopressin prohormone. To obtain clues about the mechanism of induction of FNDI by this atypical mutant we stably expressed wild type and NP87E-->stop vasopressin prohormones in (neuro)endocrine cell lines. Metabolic labeling and immunoprecipitation demonstrated reduced processing of the mutant prohormone to neurophysin. In addition, evoked secretion of neurophysin and vasopressin was diminished, suggesting that part of the mutant is retained in another intracellular compartment than the secretory granules. Indeed, immunofluorescence demonstrated accumulation of the truncated vasopressin prohormone in the endoplasmic reticulum. We conclude that the presence of the vasopressin moiety and the central conserved core of the neurophysin domain suffices for sorting and processing, but not for efficient endoplasmic reticulum exit of the vasopressin-neurophysin molecule.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Nijenhuis M,Zalm R,Burbach JP

doi

10.1016/s0303-7207(00)00288-4

keywords:

subject

Has Abstract

pub_date

2000-09-25 00:00:00

pages

55-67

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(00)00288-4

journal_volume

167

pub_type

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