Disease relevance of Freq

• The selective loss of NCS-1 during colitis may underlie the altered neural function seen in the inflamed intestine [1].
• NCS-1 was mainly present in the photoreceptor inner segments, the inner plexiform layer and the ganglion cells [2].
• To better understand how NCS-1 regulates stimulus-secretion coupling, bovine chromaffin cells were infected with Semliki Forest virus (SFV) vectors containing the rat NCS-1 gene [3].

Psychiatry related information on Freq

• 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 [4].

High impact information on Freq

• Here we show, in rat hippocampal cell cultures, that increases in the calcium binding protein neuronal calcium sensor-1 (NCS-1) can switch paired-pulse depression to facilitation without altering basal synaptic transmission or initial neurotransmitter release probability [5].
• In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway [4].
• Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium [4].
• However, spine frequency on dendrites labeled with Fl-omega-CgTx was much lower than the spine frequency on dendrites labeled with Lucifer yellow or Dil, suggesting that some spines lack N-type VDCCs [6].
• Using a new, biologically active, fluorescein conjugate of omega-conotoxin (Fl-omega-CgTx), a selective blocker of N-type VDCCs, and confocal microscopy, we have mapped the distributions of N-type VDCCs on live CA1 neurons in rat hippocampal slices [6].

Biological context of Freq

• Neuronal calcium sensor-1 gene expression is pan-neuronal [7].
• In contrast, PtdIns 4-kinase beta accumulated on the distal side which suggests that it undergoes retrograde axonal transport and unlike NCS-1 was also present in non-neuronal cells [8].
• Phosphatidylinositol 4-OH kinase is a downstream target of neuronal calcium sensor-1 in enhancing exocytosis in neuroendocrine cells [9].
• Neuronal calcium sensor-1 (NCS-1) or the originally identified homologue frequenin belongs to a superfamily of EF-hand calcium binding proteins [10].
• The possible functional role of NCS-1 in exocytosis of dense-core granules was tested using transient transfection in PC12 cells and assay of co-transfected growth hormone (GH) release [11].

Anatomical context of Freq

• Neuronal calcium sensor-1 messenger RNA is present in the dendrites of hippocampal pyramidal and granule cells, suggesting a specific role in dendritic function [7].
• Axonal transport of neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta in the adult rat sciatic nerve [8].
• Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells [10].
• Biochemical and immunohistochemical studies indicated that NCS-1 partially colocalized with the light synaptic vesicle marker synaptophysin [10].
• NCS-1 was found to have a broad distribution in the cells being partially distributed in the cytosol and associated to vesicles and tubular-like structures [10].

Associations of Freq with chemical compounds

• A model for NCS-1 function, from these data, indicates a constitutive membrane association independent of Ca(2+) [12].
• When stimulated with UTP or bradykinin, agonists to phospholipase C-linked receptors, NCS-1 enhanced the agonist-mediated elementary and global Ca2+ signaling and increased the levels of downstream signals of phosphatidylinositol 4-kinase [10].
• Taken together, NCS-1 enhances phosphoinositide turnover, resulting in enhancement of Ca2+ signaling and exocytosis [10].
• NCS-1 also enhanced exocytosis triggered by ionomycin, a Ca(2+) ionophore that bypasses K(+) and Ca(2+) channels [9].
• Plasma membrane phosphatidylinositol 4,5-bisphosphate pools were increased upon NCS-1 transfection as visualized using a phospholipase C-delta pleckstrin homology domain-green fluorescent protein construct [9].

Other interactions of Freq

• Neuronal calcium sensor (NCS) proteins including the subfamily of visinin-like-proteins (VILIPs) are involved in regulation of various signaling cascades [13].
• Mutations in NCS-1 equivalent to those that abolish the interaction of recoverin, another EF-hand-containing Ca(2+) sensor, with its downstream target rhodopsin kinase, lost their ability to enhance exocytosis [9].
• These included proteins distinct from those detected by biotinylated calmodulin, demonstrating the presence of multiple specific Ca(2+)-independent and Ca(2+)-dependent binding proteins as putative targets for NCS-1 action [12].
• Intense NCS-1 IR was colocalized with growth associated protein (GAP)-43 IR in the marginal zone and with the glutamate-aspartate transporter (GLAST) IR in the radial processes traversing the marginal zone [14].
• Dual-label Western blot analysis showed that the expression of NCS-1 relative to PGP 9.5 decreased by 50% on day 4 but returned to control by day 16 [1].

Analytical, diagnostic and therapeutic context of Freq

• We show that NCS-1 accumulates on both the distal and proximal side of the nerve ligation indicating that this protein undergoes bidirectional transport in axons [8].
• This study reports the localization of NCS-1 immunoreactivity, by Western blotting and immunohistochemistry, at the adult and developing postnatal rat neuromuscular junction [15].
• Our confocal immunofluorescence results on the whole-mount muscle and on semithin cross-sections are indicative of the localization of NCS-1 to motor axon terminals [15].
• The (45)Ca binding and isothermal titration calorimetric data show that myristoylation increases the degree of cooperativity; thus, the myristoylated NCS-1 binds Ca(2+) more strongly (with three Ca(2+) binding sites) than the non-myristoylated one (with two Ca(2+) binding sites) [16].
• Here, using in situ hybridization, we report an increased induction of the mRNA encoding NCS-1 in dentate granule cells following the induction of long-term potentiation in the awake rat [17].

References