Abstract
Store-operated Ca2+ entry (SOCE) is an ubiquitous mechanism for Ca2+ entry in eukaryotic cells. This route for Ca2+ influx is regulated by the filling state of the intracellular Ca2+ stores communicated to the plasma membrane channels by the proteins of the Stromal Interaction Molecule (STIM) family, STIM1, and STIM2. Store-dependent, STIM1-modulated, channels include the Ca2+ release-activated Ca2+ channels, comprised of subunits of Orai proteins, as well as the store-operated Ca2+ (SOC) channels, involving Orai1, and members of the canonical transient receptor potential family of proteins. Recent studies have revealed the expression of splice variants of STIM1, STIM2, and Orai1 in different cell types. While certain variants are ubiquitously expressed, others, such as STIM1L, show a more restricted expression. The splice variants for STIM and Orai1 proteins exhibit significant functional differences and reveal that alternative splicing enhance the functional diversity of STIM1, STIM2, and Orai1 genes to modulate the dynamics of Ca2+ signals.
Highlights
Eukaryotic cells finely modulate cytosolic calcium concentration ([Ca2+]c) to trigger a myriad of physiological events, from short term responses, such muscle contraction, impulse transmission, secretion, and aggregation, to long term events, including activation of transcription factors, growth and in the last instance, apoptosis, and cellular death
Be mediated by the Stromal Interaction Molecule 1 (STIM1), a protein discovered in Oritani and Kincade (1996) and known as a cell–cell interaction mediator
Concerning the Ca2+-permeable channels that conduct Store-Operated Calcium Entry (SOCE), soon after the identification of STIM1 as the endoplasmic reticulum (ER) Ca2+ sensor Orai1 was proposed as the pore-forming subunit of the Ca2+ release-activated Ca2+ (CRAC) channels (Feske et al, 2005, 2006; Mercer et al, 2006; Peinelt et al, 2006; Prakriya et al, 2006)
Summary
Eukaryotic cells finely modulate cytosolic calcium concentration ([Ca2+]c) to trigger a myriad of physiological events, from short term responses, such muscle contraction, impulse transmission, secretion, and aggregation, to long term events, including activation of transcription factors, growth and in the last instance, apoptosis, and cellular death. Store-Operated Calcium Entry (SOCE), a major mechanism for Ca2+ influx, is regulated by the filling state of the intracellular Ca2+ reservoirs, mainly the ER. STIM1 is the ER Ca2+ sensor that stimulate Ca2+ entry, triggering the activation of store-operated channels located in the PM (Roos et al, 2005; Zhang et al, 2005). Orai, together with Orai, and the PMresident STIM1 have been reported to participate in a store-independent mechanism for Ca2+ entry activated by arachidonate (Mignen et al, 2008a,b, 2009), which reveals the diversity and complexity of the regulation of Ca2+ entry in eukaryotic cells
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