Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes

Cortical endoplasmic reticulum (cER) is a permanent feature of yeast cells but occurs transiently in most animal cell types. Ist2p is a transmembrane protein that permanently localizes to the cER in yeast. When Ist2 is expressed in mammalian cells, it induces abundant cER containing Ist2. Ist2 cytop...

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Main Authors: Lavieu, Gregory (Author) , Orci, Lelio (Author) , Shi, Lei (Author) , Geiling, Michael (Author) , Ravazzola, Mariella (Author) , Wieland, Felix T. (Author) , Cosson, Pierre (Author) , Rothman, James E. (Author)
Format: Article (Journal)
Language:English
Published: March 29, 2010
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2010, Volume: 107, Issue: 15, Pages: 6876-6881
ISSN:1091-6490
DOI:10.1073/pnas.1002536107
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1002536107
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/doi/full/10.1073/pnas.1002536107
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Author Notes:Grégory Lavieu, Lelio Orci, Lei Shi, Michael Geiling, Mariella Ravazzola, Felix Wieland, Pierre Cosson, and James E. Rothman

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520 |a Cortical endoplasmic reticulum (cER) is a permanent feature of yeast cells but occurs transiently in most animal cell types. Ist2p is a transmembrane protein that permanently localizes to the cER in yeast. When Ist2 is expressed in mammalian cells, it induces abundant cER containing Ist2. Ist2 cytoplasmic C-terminal peptide is necessary and sufficient to induce cER. This peptide sequence resembles classic coat protein complex I (COPI) coatomer protein-binding KKXX signals, and indeed the dimerized peptide binds COPI in vitro. Controlled dimerization of this peptide induces cER in cells. RNA interference experiments confirm that coatomer is required for cER induction in vivo, as are microtubules and the microtubule plus-end binding protein EB1. We suggest that Ist2 dimerization triggers coatomer binding and clustering of this protein into domains that traffic at the microtubule growing plus-end to generate the cER beneath the plasma membrane. Sequences similar to the Ist2 lysine-rich tail are found in mammalian STIM proteins that reversibly induce the formation of cER under calcium control. 
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