STIM Proteins: An Ever-Expanding Family

Grabmayr, Herwig; Romanin, Christoph; Fahrner, Marc

doi:10.3390/ijms22010378

Cited by 33 publications

(51 citation statements)

References 113 publications

(252 reference statements)

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“…Subsequently, STIM1 proteins undergo a conformational change and oligomerize [ 37 , 38 , 42 , 43 ]. Store depletion-induced structural changes propagate from its N-terminal strand to its single TM domain and finally to the C-terminus [ 44 , 45 , 46 , 47 , 48 ]. In particular, STIM1 C-terminus adopts a tight conformation in the quiescent state, which fully extends upon activation to bind to Orai channels in the plasma membrane [ 45 , 49 , 50 , 51 ].…”

Section: Overview Of Store-operated Ca 2+ Entrymentioning

confidence: 99%

Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology

Tiffner

Derler

2021

IJMS

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Ca2+ ion channels are critical in a variety of physiological events, including cell growth, differentiation, gene transcription and apoptosis. One such essential entry pathway for calcium into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel. It consists of the Ca2+ sensing protein, stromal interaction molecule 1 (STIM1) located in the endoplasmic reticulum (ER) and a Ca2+ ion channel Orai in the plasma membrane. The Orai channel family includes three homologues Orai1, Orai2 and Orai3. While Orai1 is the “classical” Ca2+ ion channel within the CRAC channel complex and plays a universal role in the human body, there is increasing evidence that Orai2 and Orai3 are important in specific physiological and pathophysiological processes. This makes them an attractive target in drug discovery, but requires a detailed understanding of the three Orai channels and, in particular, their differences. Orai channel activation is initiated via Ca2+ store depletion, which is sensed by STIM1 proteins, and induces their conformational change and oligomerization. Upon STIM1 coupling, Orai channels activate to allow Ca2+ permeation into the cell. While this activation mechanism is comparable among the isoforms, they differ by a number of functional and structural properties due to non-conserved regions in their sequences. In this review, we summarize the knowledge as well as open questions in our current understanding of the three isoforms in terms of their structure/function relationship, downstream signaling and physiology as well as pathophysiology.

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Section: Overview Of Store-operated Ca 2+ Entrymentioning

confidence: 99%

Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology

Tiffner

Derler

2021

IJMS

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“…STIM1 stays at a closed state when ER lumen is filled with Ca 2+ and transitions to an open state when Ca 2+ in the ER lumen is decreased [54]. The Ca 2+ -sensitive domain in the STIM N-terminal senses Ca 2+ level of ER ranging from 100 to 400 µM [52,55], and the C-terminal of STIM interacts with Orai to form CRAC channel to induce Ca 2+ influx [52,56]. As mentioned above, the interactions between STIM1 and Orai1 regulate physiological and pathological functions [35,39,50].…”

Section: Stimmentioning

confidence: 99%

Cross-Talk between Mechanosensitive Ion Channels and Calcium Regulatory Proteins in Cardiovascular Health and Disease

Wang

Shi

Tong

2021

IJMS

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Mechanosensitive ion channels are widely expressed in the cardiovascular system. They translate mechanical forces including shear stress and stretch into biological signals. The most prominent biological signal through which the cardiovascular physiological activity is initiated or maintained are intracellular calcium ions (Ca2+). Growing evidence show that the Ca2+ entry mediated by mechanosensitive ion channels is also precisely regulated by a variety of key proteins which are distributed in the cell membrane or endoplasmic reticulum. Recent studies have revealed that mechanosensitive ion channels can even physically interact with Ca2+ regulatory proteins and these interactions have wide implications for physiology and pathophysiology. Therefore, this paper reviews the cross-talk between mechanosensitive ion channels and some key Ca2+ regulatory proteins in the maintenance of calcium homeostasis and its relevance to cardiovascular health and disease.

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“…Genes upregulated in Type-2. Depletion of Ca 2+ in the endoplasmic reticulum (ER) activates the stromal interaction molecule (STIM) proteins, which subsequently activate the Ca 2+ releaseactivated Ca 2+ (CRAC) channels on the plasma membrane via the key subunit of CRAC channel, Orai1 [24][25][26][27] . We report Type-2 upregulation of the CRAC channel regulator 2A gene, Cracr2a, as well as the serine/threonine protein kinase gene, Sgk1, which activates STIM1 and Orai1 and thus enhances store-operated Ca 2+ entry (SOCE) 28 .…”

Section: Transcriptomic Differences Between Type-1 and Type-2 Neuronsmentioning

confidence: 99%

Transcriptomes of Electrophysiologically Recorded Dbx1-derived Inspiratory Neurons of the preBötzinger Complex in Neonatal Mice

Kallurkar

Picardo

Sugimura

et al. 2021

Preprint

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Breathing depends on interneurons in the preBötzinger complex (preBötC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBötC neurons. In a slice model of breathing with ~5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBötC neurons activate 100-300 ms prior to Type-2 neurons, putatively specialized for output pattern, and 300-500 ms prior to the inspiratory motor output. We sequenced Type-1 and Type-2 transcriptomes and identified differential expression of 123 genes including ionotropic receptors (Gria3 and Gabra1) that may explain their preinspiratory activation profiles and Ca2+ signaling (Cracr2a, Sgk1) involved in inspiratory and sigh bursts. Surprisingly, neuropeptide receptors that influence breathing (e.g., μ-opioid and bombesin-like peptide receptors) were only sparsely expressed, which suggests that cognate peptides and opioid drugs exert their profound effects on a small fraction of the preBötC core. These data in the public domain help explain the neural origins of breathing.

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STIM Proteins: An Ever-Expanding Family

Cited by 33 publications

References 113 publications

Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology

Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology

Cross-Talk between Mechanosensitive Ion Channels and Calcium Regulatory Proteins in Cardiovascular Health and Disease

Transcriptomes of Electrophysiologically Recorded Dbx1-derived Inspiratory Neurons of the preBötzinger Complex in Neonatal Mice

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