{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:05:25Z","timestamp":1783101925199,"version":"3.54.6"},"reference-count":28,"publisher":"The Company of Biologists","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,11,1]]},"abstract":"<jats:p>Autosomal dominant neurohypophyseal diabetes insipidus results from mutations in the precursor protein of the antidiuretic hormone arginine vasopressin. Mutant prohormone is retained in the endoplasmic reticulum of vasopressinergic neurons and causes their progressive degeneration by an unknown mechanism. Here, we show that several dominant pro-vasopressin mutants form disulfide-linked homo-oligomers and develop large aggregations visible by immunofluorescence and immunogold electron microscopy, both in a fibroblast and a neuronal cell line. Double-labeling showed the pro-vasopressin aggregates to colocalize with the chaperone calreticulin, indicating that they originated from the endoplasmic reticulum. The aggregates revealed a remarkable fibrillar substructure. Bacterially expressed and purified mutant pro-vasopressin spontaneously formed fibrils under oxidizing conditions. Mutagenesis experiments showed that the presence of cysteines, but no specific single cysteine, is essential for disulfide oligomerization and aggregation in vivo. Our findings assign autosomal dominant diabetes insipidus to the group of neurodegenerative diseases associated with the formation of fibrillar protein aggregates.<\/jats:p>","DOI":"10.1242\/jcs.051136","type":"journal-article","created":{"date-parts":[[2009,10,14]],"date-time":"2009-10-14T03:59:58Z","timestamp":1255492798000},"page":"3994-4002","source":"Crossref","is-referenced-by-count":64,"title":["Dominant pro-vasopressin mutants that cause diabetes insipidus form disulfide-linked fibrillar aggregates in the endoplasmic reticulum"],"prefix":"10.1242","volume":"122","author":[{"given":"Julia","family":"Birk","sequence":"first","affiliation":[{"name":"Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Friberg","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Prescianotto-Baschong","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Spiess","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Rutishauser","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021111216223122500_REF1","doi-asserted-by":"crossref","unstructured":"Appenzeller-Herzog, C., Nyfeler, B., Burkhard, P., Santamaria, I., Lopez-Otin, C. and Hauri, H. 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(1999). Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation. J. Clin. Endocrinol. Metab.84, 2933-2941.","DOI":"10.1210\/jcem.84.8.5869"},{"key":"2021111216223122500_REF28","doi-asserted-by":"crossref","unstructured":"Willcutts, M. D., Felner, E. and White, P. C. (1999). Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin. Hum. Mol. 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