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

Abstract

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

TMEM110 regulates the maintenance and remodeling of mammalian ER–plasma membrane junctions competent for STIM–ORAI signaling

“…5A), in HeLa cells depleted of TMEM110 or in HEK293 cells entirely lacking the protein. This fragment has been shown previously to increase ER-plasma membrane junctional area in mammalian cells (29). Initial experiments confirmed the expected cortical localization of Ist2 expressed in HeLa cells (Fig.…”

Lipid Transport between the Endoplasmic Reticulum and Mitochondria

“…Interestingly, MAM harbor a number of lipid synthesizing enzymes (Gaigg et al 1994). Recently, molecular components governing membrane contact between the two organelles were identified (Dolman et al 2005;Csordás et al 2006;de Brito and Scorrano 2008;Kornmann et al 2009;Friedman et al 2010;Lavieu et al 2010), although the specific role of these components in lipid translocation is not yet clear.…”

Morphological and functional aspects of STIM1-dependent assembly and disassembly of store-operated calcium entry complexes

“…The pre-cortical ER is frequently found extending along microtubules, implying a possible role of microtubule in the formation of the cortical ER [38]. A yeast ER transmembrane protein resembling STIM1, Ist2, also induces the formation of cortical ER upon dimerization, and Ist2-mediated cortical ER formation was shown to require microtubules and EB1 [39]. Microtubules are not required for SOCE activation, however, because microtubule depolymerization with taxol or nocozadole does not abrogate SOCE and only disturbs the movement of STIM1 comets occurring before the Ca 2 + depletion of the ER [28,40].…”