Disease relevance of FREQ

• IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis [1].
• We identified a taxol binding protein, neuronal Ca(2+) sensor 1 (NCS-1), a Ca(2+) binding protein that interacts with the inositol 1,4,5-trisphosphate receptor from a human brain cDNA phage display library [2].
• This study evaluated the preoperative use of a newly developed 7.5 MHz front-loading ultrasound probe (FLUP) for local staging of rectal cancer [3].
• RESULTS: The FLUP proved to be satisfactory, with respect to maneuverability, for traversing stenosis and accurate recognition of small tumors under direct endoscopic control [3].
• Application of NCS-1 cells to a panel of monoclonal antibodies recognizing melanocytic differentiation antigens showed that they corresponded approximately to highly differentiated melanoma cells [4].

Psychiatry related information on FREQ

• Interaction between variation in the D2 dopamine receptor (DRD2) and the neuronal calcium sensor-1 (FREQ) genes in predicting response to nicotine replacement therapy for tobacco dependence [5].
• These levels of neuronal calcium sensor-1 were not influenced by age, gender, hemisphere, cause of death, postmortem period, alcohol consumption, or antipsychotic and mood stabilizing medications [6].
• To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders [7].

High impact information on FREQ

• In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway [7].
• Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium [7].
• We propose that NCS-1 is a novel survival-promoting factor up-regulated in injured neurons that mediates the GDNF survival signal via the phosphatidylinositol 3-kinase-Akt pathway [8].
• In this study, we demonstrate that an EF-hand Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1), one of the key proteins for various neuronal functions, also acts as an important survival factor [8].
• Overexpression of NCS-1 rendered cultured neurons more tolerant to cell death caused by several kinds of stressors, whereas the dominant-negative mutant (E120Q) accelerated it [8].

Chemical compound and disease context of FREQ

• Enzyme-linked immunoadsorbent assay revealed that NCS-1 cells expressed a 75-kDa glycoprotein which was identified as a marker of highly differentiated melanoma cells [4].

Biological context of FREQ

• This result suggests that the interaction between variation in the DRD2 and FREQ genes, which both encode components of the D2 dopamine receptor signal transduction pathway, impacts the efficacy of NRT [5].
• The localization of NCS-1 was unaffected by mutations in all functional EF hands, indicating that its localization was independent of Ca(2+) [9].
• In striatum, NCS-1 and D2 receptors were found to colocalize within sites of synaptic transmission and in close proximity to intracellular calcium stores [10].
• NCS-1-D2 receptor interaction may serve to couple dopamine and calcium signaling pathways, thereby providing a critical component in the regulation of dopaminergic signaling in normal and diseased brain [10].
• Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation [10].

Anatomical context of FREQ

• Immunoprecipitation and green fluorescent protein imaging show that KChIPs (but not NCS-1) effectively bind to Kv4.3 protein and localize at the plasma membrane when channel proteins are coexpressed [11].
• We demonstrate that the dorsolateral prefrontal cortex in schizophrenia and bipolar cases from the Stanley Foundation Neuropathology Consortium display significantly elevated levels of the D2 dopamine receptor desensitization regulatory protein, neuronal calcium sensor-1 [6].
• Human neuronal calcium sensor-1 shows the highest expression level in cerebral cortex [12].
• Among the brain regions, the expression level of NCS-1 in cerebral cortex is the highest, which is about six times higher than the average level of the whole brain and a hundred times higher than the spinal cord [12].
• In the 12 different anatomical regions of human brain, the expression level of NCS-1 is very high in the temporal lobe, occipital pole, frontal lobe, thalamus, amygdala and hippocampus; moderate in cerebellum, putamen, caudate nucleus; low in the medulla, substantia nigra and the lowest in corpus callosum [12].

Associations of FREQ with chemical compounds

• Remarkably, although NCS-1 and its non-mammalian homologue, frequenin, are members of a highly conserved EF-hand Ca(2+) binding protein family, our data show that IL1RAPL interacts only with NCS-1 through its specific C-terminal domain [1].
• Recombinant PI4Kbeta, but not its glutathione S-transferase-fused form, showed enhanced PI kinase activity when incubated with recombinant NCS-1, but only if the latter was myristoylated [13].
• Transfection of PI4Kbeta and NCS-1 had no effect on basal PIP synthesis in permeabilized COS-7 cells, but it increased the wortmannin-sensitive [(32)P]phosphate incorporation into phosphatidylinositol 4-phosphate during Ca(2+)-induced phospholipase C activation [13].
• Consistently, NCS-1 also enhances, whereas both KD-PI4Kbeta and FAPP1-PH domain inhibit, Fc epsilonRI-induced release of arachidonic acid/metabolites, a downstream target of ERK1/2 in mast cells [14].
• We show further that overexpression of NCS-1 in RBL-2H3 cells stimulates the catalytic activity of PI4Kbeta, increases IgE receptor (FcepsilonRI)-triggered hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)), and stimulates FcepsilonRI-triggered, but not Ca(2+) ionophore-triggered, exocytosis [15].

Physical interactions of FREQ

• These results together indicate that NCS-1 is able to interact with PI4Kbeta also in mammalian cells and may play a role in the regulation of this enzyme in specific cellular compartments affecting vesicular trafficking [13].
• CPZ binds myristoylated as well as non-myristoylated NCS-1 in Ca(2+)-dependent manner, with dynamic interaction to myristoylated protein [16].

Other interactions of FREQ

• Upon the elevation of intracellular Ca(2+), hippocalcin rapidly translocated to the same perinuclear compartment as NCS-1 [9].
• Similarly, in vitro translated NCS-1, but not its myristoylation-defective mutant, was found associated with recombinant- or in vitro translated PI4Kbeta in PI4Kbeta-immunoprecipitates [13].
• Furthermore, schizophrenia-associated alterations in the levels of calcyon and NCS-1 messages were correlated [17].
• Mutant NCS-1 does not inhibit surface-expression of TRPC5 but generally suppresses channel activity, irrespective of whether it is evoked by carbachol, store depletion, lanthanides or elevated intracellular calcium [18].

Analytical, diagnostic and therapeutic context of FREQ

• Allele-specific PCR studies of selected subjects indicated the existence of the CYP2D6B allele (freq = 0.17; C.I.95% = 0.085, 0.29; n = 30 unrelated subjects), in addition to the wild-type [19].
• DMB parameters (mean DMB, DMB Freq. Max. and Heterogeneity Index of the individual distributions of DMB) were measured using quantitative microradiography in cortical, cancellous, and total bone and expressed as g mineral/cm(3) bone [20].
• A clear cell sarcoma (CCS) cell line, designated as NCS-1, was established in monolayer culture from a xenograft line originating from a metastatic CCS [4].
• Recently, a linear, analytical distributed model for capacitive micromachined ultrasonic transducers (CMUTs) was presented, and an electromechanical equivalent circuit based on the theory reported was used to describe the behavior of the transducer [IEEE Trans. Ultrason. Ferroelectr. Freq. Control 49, 159-168 (2002)] [21].

References