Ca 2+ inflow from the external milieu is mediated by voltage-operated Ca 2+ channels (VOCCs) or by receptor-operated channels (ROCs Figure Figure1 1), such as the glutamate-sensitive N-methyl- D-aspartate receptors (NMDARs Catterall, 2011 Paoletti et al., 2013). As virtually any other cell type ( Clapham, 2007 Moccia et al., 2014c), neurons use both intra- and extracellular Ca 2+ sources which may interact to control Ca 2+-dependent processes ( Berridge, 1998). Neurons possess a highly developed Ca 2+ machinery that delivers a multitude of Ca 2+ signals precisely tailored at regulating specific neuronal functions ( Berridge, 1998). Finally, we evaluate the involvement of Stim and Orai proteins in severe neurodegenerative and neurological disorders, such as Alzheimer’s disease and epilepsy. Besides, we highlighted the possibility that SOCE also controls neuronal excitation and regulate synaptic plasticity. We examine the functions regulated by SOCE in neurons, where this pathway is activated under resting conditions to refill the ER, control spinogenesis and regulate gene transcription. Herein, we survey current knowledge about the neuronal distribution of Stim and Orai proteins in rodent and human brains we further discuss that Orai2 is the main pore-forming subunit of CRAC channels in central neurons, in which it may be activated by either Stim1 or Stim2 depending on species, brain region and physiological stimuli. Nevertheless, recent work has unveiled that Stim1–2 and Orai1-2, but not Orai3, proteins are also expressed and mediate SOCE in neurons. Ca 2+ inflow in neurons has long been exclusively ascribed to voltage-operated and receptor-operated channels. Their paralogs, Stim2, Orai2 and Orai3, support SOCE in heterologous expression systems, but their physiological role is still obscure. SOCE is activated following the depletion of the endogenous Ca 2+ stores, which are mainly located within the endoplasmic reticulum (ER), to replete the intracellular Ca 2+ reservoir and engage specific Ca 2+-dependent processes, such as proliferation, migration, cytoskeletal remodeling, and gene expression. Stim1 and Orai1 are ubiquitous proteins that have long been known to mediate Ca 2+ release-activated Ca 2+ (CRAC) current (I CRAC) and store-operated Ca 2+ entry (SOCE) only in non-excitable cells.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |