Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus

The Journal of Clinical Investigation
M ItoM O Lively

Abstract

A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals.

References

Sep 1, 1995·Endocrinology and Metabolism Clinics of North America·G L Robertson
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·L K HansenG L Robertson
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y LiC Y Kang
Jan 1, 1995·Annual Review of Medicine·T M FujiwaraD G Bichet
Dec 3, 2011·Journal of the American Society of Nephrology : JASN·Jiqiu WangGuang Ning
May 10, 2016·Best Practice & Research. Clinical Endocrinology & Metabolism·J RutishauserP Kopp
May 23, 2006·Seminars in Nephrology·Jane H Christensen, S Rittig
Mar 26, 1999·American Journal of Human Genetics·C E JacksonJ M Puck
Mar 8, 2016·Traffic·Lars EllgaardIneke Braakman
Jan 10, 2003·Clinical Endocrinology·Wolfanga L BosonBernardo Wajchenberg
Aug 7, 1999·The Journal of Biological Chemistry·G ZanussoN Singh
Jul 12, 2002·Human Mutation·Irene L AndrulisCooperative Family Registry for Breast Cancer studies
May 23, 2003·Genes and Immunity·H A WhittingtonA B Millar
Mar 5, 2004·The Journal of Biological Chemistry·Michael A FribergJ Rutishauser
Oct 16, 1999·The Journal of Clinical Endocrinology and Metabolism·T SunthornthepvarakulS Ngowngarmratana
Feb 19, 1998·The Journal of Clinical Endocrinology and Metabolism·C HeppnerD Müller-Wieland
Mar 6, 2019·Journal of Clinical Medicine·Young Jun ChaiSang Wan Kim
Mar 20, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Masayuki HayashiYutaka Oiso

Citations

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S O BrennanP M George
Aug 24, 1990·Cell·R D Klausner, R Sitia
Jun 11, 1986·Nucleic Acids Research·G von Heijne
Jul 5, 1985·Journal of Molecular Biology·G von Heijne
Jan 25, 1980·Science·M J BrownsteinH Gainer
Jun 1, 1983·European Journal of Biochemistry·G von Heijne
Jan 1, 1982·The Journal of Pediatrics·P B KaplowitzG L Robertson
Jan 1, 1981·Postgraduate Medical Journal·P H Baylis, G L Robertson
Oct 30, 1981·Biochemical and Biophysical Research Communications·R IvellD Richter

Related Concepts

Inborn Errors of Metabolism
Pathogenic Aspects
Pathogenesis
Exons
Genome
Pitressin
Microsomes
Transcription, Genetic
Antidiuretic Hormone Measurement
Cytokinesis of the Fertilized Ovum

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Synapse Loss as Therapeutic Target in MS

As we age, the number of synapses present in the human brain starts to decline, but in neurodegenerative diseases this occurs at an accelerated rate. In MS, it has been shown that there is a reduction in synaptic density, which presents a potential target for treatment. Here is the latest research on synapse loss as a therapeutic target in MS.

Artificial Intelligence in Cardiac Imaging

Artificial intelligence (ai) techniques are increasingly applied to cardiovascular (cv) medicine in cardiac imaging analysis. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Social Learning

Social learning involves learning new behaviors through observation, imitation and modeling. Follow this feed to stay up to date on the latest research.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Single Cell Chromatin Profiling

Techniques like ATAC-seq and CUT&Tag have the potential to allow single cell profiling of chromatin accessibility, histones, and TFs. This will provide novel insight into cellular heterogeneity and cell states. Discover the latest research on single cell chromatin profiling here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.