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The intramembrane protease SPP impacts morphology of the endoplasmic reticulum by triggering degradation of morphogenic proteins

The endoplasmic reticulum (ER), as a multifunctional organelle, plays crucial roles in lipid biosynthesis and calcium homeostasis as well as the synthesis and folding of secretory and membrane proteins. Therefore, it is of high importance to maintain ER homeostasis and to adapt ER function and morph...

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Main Authors: Avci, Dönem (Author) , Malchus, Nicole Susanne (Author) , Heidasch, Ronny (Author) , Lorenz, Holger (Author) , Richter, Karsten (Author) , Neßling, Michelle (Author) , Lemberg, Marius (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: The journal of biological chemistry
Year: 2018, Volume: 294, Issue: 8, Pages: 2786-2800
ISSN:1083-351X
DOI:10.1074/jbc.RA118.005642
Online Access:Verlag, Volltext: https://doi.org/10.1074/jbc.RA118.005642
Verlag, Volltext: http://www.jbc.org/content/294/8/2786
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Author Notes:Dönem Avci, Nicole S. Malchus, Ronny Heidasch, Holger Lorenz, Karsten Richter, Michelle Neßling, and Marius K. Lemberg
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Summary:The endoplasmic reticulum (ER), as a multifunctional organelle, plays crucial roles in lipid biosynthesis and calcium homeostasis as well as the synthesis and folding of secretory and membrane proteins. Therefore, it is of high importance to maintain ER homeostasis and to adapt ER function and morphology to cellular needs. Here, we show that signal peptide peptidase (SPP) modulates the ER shape through degradation of morphogenic proteins. Elevating SPP activity induces rapid rearrangement of the ER and formation of dynamic ER clusters. Inhibition of SPP activity rescues the phenotype without the need for new protein synthesis, and this rescue depends on a pre-existing pool of proteins in the Golgi. With the help of organelle proteomics, we identified certain membrane proteins to be diminished upon SPP expression and further show that the observed morphology changes depend on SPP-mediated cleavage of ER morphogenic proteins, including the SNARE protein syntaxin-18. Thus, we suggest that SPP-mediated protein abundance control by a regulatory branch of ER-associated degradation (ERAD-R) has a role in shaping the early secretory pathway.
Item Description:First published on December 21, 2018
Gesehen am 15.04.2019
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.RA118.005642

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