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Studies of Structure–Function and Subunit Composition of Orai/STIM Channel
| Content Provider | Scilit |
|---|---|
| Author | Fahrner, Marc Schindl, Rainer Romanin, Christoph |
| Copyright Year | 2017 |
| Description | Book Name: Calcium Entry Channels in Non-Excitable Cells |
| Abstract | Among all known second messengers in eukaryotic cells, $Ca^{2+}$ is one of the most versatile and is involved in a multitude of physiological and cellular processes including cell proliferation, growth, gene expression, muscle contraction, and exocytosis/secretion [1,2]. To act as an intracellular signal molecule, $Ca^{2+}$ has to enter the cell at specific physiological/cellular situations and time points. One major pathway that allows $Ca^{2+}$ entry into the cells involves the $Ca^{2+}$ release–activated $Ca^{2+}$ (CRAC) channels, which belong to the group of store-operated channels (SOC) [3–14]. In the beginning of the CRAC/SOC channel analysis, these channels were studied and characterized using mainly cells of the immune system, that is, T-lymphocytes and mast cells [9,10,14,15]. Finally, in 2005–2006, the major key players forming the functional CRAC channel complex were identified [16–27]: first, the stromal interaction molecule (STIM), which represents the $Ca^{2+}$ sensor in the endoplasmic reticulum (ER), and second, Orai, which is located in the plasma membrane (PM) and builds the ion-conducting transmembrane (TM) protein complex. Feske and colleagues [16] had studied a defect in CRAC channel function linked to one form of 26hereditary severe combined immune deficiency (SCID) syndrome, which allowed the identification of the Orai1 (also initially termed CRACM1) channel protein and its mutated form (Orai1 R91W) in SCID patients. By successfully employing and combining a modified linkage analysis with single-nucleotide polymorphism arrays and a Drosophila RNA interference screen, light was shed on the gene and protein that forms the $Ca^{2+}$ conducting CRAC channel [16]. Furthermore, the search for homologous proteins using a sequence database research revealed Orai1, Orai2, and Orai3 in higher vertebrates. The three members of the Orai protein family have been analyzed with bioinformatics methods showing that they represent TM proteins with 4 PM spanning domains connected by one intracellular and two extracellular loops and cytosolic N-and C-termini [16,20,28,29]. Several research groups have concentrated on the electrophysiological examination and characterization of Orai proteins revealing the typical high $Ca^{2+}$ selectivity and low single-channel conductance, concluding that these proteins unequivocally represent the pore-forming entity of the CRAC channel. |
| Related Links | https://content.taylorfrancis.com/books/download?dac=C2015-0-66093-7&isbn=9781315152592&doi=10.1201/9781315152592-2&format=pdf |
| Ending Page | 50 |
| Page Count | 26 |
| Starting Page | 25 |
| DOI | 10.1201/9781315152592-2 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2017-07-14 |
| Access Restriction | Open |
| Subject Keyword | Book Name: Calcium Entry Channels in Non-Excitable Cells Critical Care Medicine Gene Expression Intracellular |
| Content Type | Text |
| Resource Type | Chapter |
