Alternative splicing regulates the endoplasmic reticulum localization or secretion of soluble secreted endopeptidase

The Journal of Biological Chemistry
S B RaharjoM Matsuo

Abstract

A subfamily of zinc metalloproteases, represented by Neutral endopeptidase (EC ) and endothelin-converting enzyme, is involved in the metabolism of a variety of biologically active peptides. Recently, we cloned and characterized a novel member of this metalloprotease family termed soluble secreted endopeptidase (SEP), which hydrolyzes many vasoactive peptides. Here we report that alternative splicing of the mouse SEP gene generates two polypeptides, SEP(Delta) and SEP. After synthesis, both isoforms are inserted into the endoplasmic reticulum (ER) as type II membrane proteins. SEP(Delta) then becomes an ER resident, whereas SEP, which differs by only the presence of 23 residues at the beginning of its luminal domain, is proteolytically cleaved by membrane secretase(s) in the ER and transported into the extracellular compartment. An analysis of the chimeric proteins between SEP(Delta) and bovine endothelin-converting enzyme-1b (bECE-1b) demonstrated that the retention of SEP(Delta) in the ER is mediated by the luminal domain. In addition, the dissection of the chimeric bECE-1b/SEP insertion showed that its insertion domain is obviously responsible for its secretion. A series of mutagenesis in this region revealed that the minima...Continue Reading

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Citations

Apr 20, 2002·The Biochemical Journal·Christiane RoseTanja Ouimet
Jun 27, 2003·Journal of Cardiovascular Pharmacology·Daiji IsakaMasafumi Matsuo
May 4, 2004·Molecular and Cellular Biology·Mélanie CarpentierJean Charron
Nov 30, 2011·Journal of Neurochemistry·Natalia N NalivaevaAnthony J Turner
Jan 20, 2005·Gene·Stefan StammHermona Soreq
Jan 13, 2011·The American Journal of Pathology·Daniel HafezRobert A Marr
Jun 11, 2002·Biochemical and Biophysical Research Communications·Shoko IkedaMasafumi Matsuo
Aug 29, 2014·Frontiers in Aging Neuroscience·Robert A Marr, Daniel M Hafez
Oct 7, 2004·International Review of Cytology·Nathalie MacoursRoger Huybrechts
Apr 20, 2010·The Journal of Biological Chemistry·Sakeneh ZraikaSteven E Kahn
Oct 17, 2003·Coronary Artery Disease·Matthias BartonChristian C Haudenschild
Nov 26, 2019·Biochemistry. Biokhimii︠a︡·E E FeyginaA G Semenov

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