The STIM1–ORAI1 microdomain

Hogan, Patrick G.

doi:10.1016/j.ceca.2015.07.001

Cited by 86 publications

(102 citation statements)

References 113 publications

(152 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Even subtle structural changes in existing junctions can shape calcium signaling both by altering the local landscape for calcium diffusion, and hence the local calcium concentration profile, and by setting constraints on the positioning of calcium-handling proteins such as SERCA and PMCA (6). Recent mechanistic studies have highlighted the dynamic changes attributable to E-Syt proteins and their partners (11,12,22,30).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Quintana

Vangipurapu

Farber-Katz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The stromal interaction molecule (STIM)–ORAI calcium release-activated calcium modulator (ORAI) pathway controls store-dependent calcium entry, a major mechanism of physiological calcium signaling in mammalian cells. The core elements of the pathway are the regulatory protein STIM1, located in the endoplasmic reticulum (ER) membrane, the calcium channel ORAI1 in the plasma membrane, and sites of close contact between the ER and the plasma membrane that permit the two proteins to interact. Research on calcium signaling has centered on STIM1, ORAI1, and a few proteins that directly modulate STIM–ORAI function. However, little is known about proteins that organize ER–plasma membrane junctions for STIM–ORAI-dependent calcium signaling. Here, we report that an ER-resident membrane protein identified in a previous genome-wide RNAi screen, transmembrane protein 110 (TMEM110), regulates the long-term maintenance of ER–plasma membrane junctions and the short-term physiological remodeling of the junctions during store-dependent calcium signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The junctions establish a 15-to 20-nm spacing between membranes that STIM1 can bridge to interact with ORAI1 (5). At the same time, the individual junctions define a specialized local geometry that contributes to shaping cellular calcium signaling (6,7).…”

mentioning

confidence: 99%

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

Quintana

Vangipurapu

Farber-Katz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Orai channels are highly Ca 2ϩ -selective plasma membrane (PM) 4 channels activated through an elaborate intermembrane coupling mechanism by the Ca 2ϩ -sensing STIM proteins of the endoplasmic reticulum (ER) (1)(2)(3)(4)(5)(6). Alterations in the function of Orai channels and STIM proteins are implicated in a large number of immunological, muscular, and inflammatory disease states (1,(7)(8)(9).…”

Section: Entry Moreover Each Orai1 Concatemer Mediated Camentioning

confidence: 99%

“…In particular, the multimeric assembly of the Orai1 channel, the most commonly expressed of the three-member mammalian Orai channel family, has remained a contentious issue (1,2,5,6,22,23). Recent crystallographic evidence reveals that Drosophila Orai has a hexameric subunit structure, a result reinforced by cross-linking and chromatographic evidence (22).…”

Section: Entry Moreover Each Orai1 Concatemer Mediated Camentioning

confidence: 99%

The Orai1 Store-operated Calcium Channel Functions as a Hexamer

Cai

Zhou

Nwokonko

et al. 2016

Journal of Biological Chemistry

102

View full text Add to dashboard Cite

Edited by Roger ColbranOrai channels mediate store-operated Ca 2؉ signals crucial in regulating transcription in many cell types, and implicated in numerous immunological and inflammatory disorders. Despite their central importance, controversy surrounds the basic subunit structure of Orai channels, with several biochemical and biophysical studies suggesting a tetrameric structure yet crystallographic evidence indicating a hexamer. We systematically investigated the subunit configuration of the functional Orai1 channel, generating a series of tdTomato-tagged concatenated Orai1 channel constructs (dimers to hexamers) expressed in CRISPR-derived ORAI1 knock-out HEK cells, stably expressing STIM1-YFP. Surface biotinylation demonstrated that the fulllength concatemers were surface membrane-expressed. Unexpectedly, Orai1 dimers, trimers, tetramers, pentamers, and hexamers all mediated similar and substantial store-operated Ca 2؉ entry. Moreover, each Orai1 concatemer mediated Ca 2؉ currents with inward rectification and reversal potentials almost identical to those observed with expressed Orai1 monomer. In Orai1 tetramers, subunit-specific replacement with Orai1 E106A "pore-inactive" subunits revealed that functional channels utilize only the N-terminal dimer from the tetramer. In contrast, Orai1 E106A replacement in Orai1 hexamers established that all the subunits can contribute to channel formation, indicating a hexameric channel configuration. The critical Ca 2؉ selectivity filter-forming Glu-106 residue may mediate Orai1 channel assembly around a central Ca 2؉ ion within the pore. Thus, multiple E106A substitutions in the Orai1 hexamer may promote an alternative "trimer-of-dimers" channel configuration in which the C-terminal E106A subunits are excluded from the hexameric core. Our results argue strongly against a tetrameric configuration for Orai1 channels and indicate that the Orai1 channel functions as a hexamer.

show abstract

“…For instance, Ca 2þ signaling in T-cells and mast cells is strongly dictated by the gating of PM resident Ca 2þ selective channel protein, ORAI1 by activated ER resident Ca 2þ sensor, STIM1. Many important mechanisms that modulate STIM1-ORAI1 interaction within ER-PM junction of $7-30 nm have remain incomprehensible, 6 but their implications on Ca 2þ signaling in various cells 7 have a profound biological significance. Realizing tightly regulated membrane-restricted nanoscale domains with spatial control of reconstituted (or membrane localized) functional proteins demand engineered multifunctional systems at the interface of biology and materials physics.…”

mentioning

confidence: 99%

Multifunctional-layered materials for creating membrane-restricted nanodomains and nanoscale imaging

Srinivasan

2016

Applied Physics Letters

View full text Add to dashboard Cite

Experimental platform that allows precise spatial positioning of biomolecules with an exquisite control at nanometer length scales is a valuable tool to study the molecular mechanisms of membrane bound signaling. Using micromachined thin film gold (Au) in layered architecture, it is possible to add both optical and biochemical functionalities in in vitro. Towards this goal, here, I show that docking of complementary DNA tethered giant phospholiposomes on Au surface can create membrane-restricted nanodomains. These nanodomains are critical features to dissect molecular choreography of membrane signaling complexes. The excited surface plasmon resonance modes of Au allow label-free imaging at diffraction-limited resolution of stably docked DNA tethered phospholiposomes, and lipid-detergent bicelle structures. Such multifunctional building block enables realizing rigorously controlled in vitro set-up to model membrane anchored biological signaling, besides serving as an optical tool for nanoscale imaging. V C 2016 AIP Publishing LLC.

show abstract

The STIM1–ORAI1 microdomain

Abstract: Graphical Abstract

Cited by 86 publications

References 113 publications

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

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

The Orai1 Store-operated Calcium Channel Functions as a Hexamer

Multifunctional-layered materials for creating membrane-restricted nanodomains and nanoscale imaging

Contact Info

Product

Resources

About