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Gene Review

Ncs1  -  neuronal calcium sensor 1

Rattus norvegicus

Synonyms: Flup, Freq, Frequenin homolog, Frequenin-like protein, Frequenin-like ubiquitous protein, ...
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Disease relevance of Freq


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


Anatomical context of Freq


Associations of Freq with chemical compounds


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


  1. Intestinal inflammation modulates expression of the synaptic vesicle protein neuronal calcium sensor-1. Lourenssen, S., Jeromin, A., Roder, J., Blennerhassett, M.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  2. Distribution pattern of three neural calcium-binding proteins (NCS-1, VILIP and recoverin) in chicken, bovine and rat retina. De Raad, S., Comte, M., Nef, P., Lenz, S.E., Gundelfinger, E.D., Cox, J.A. Histochem. J. (1995) [Pubmed]
  3. Alterations in exocytosis induced by neuronal Ca2+ sensor-1 in bovine chromaffin cells. Pan, C.Y., Jeromin, A., Lundstrom, K., Yoo, S.H., Roder, J., Fox, A.P. J. Neurosci. (2002) [Pubmed]
  4. Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium. Schlecker, C., Boehmerle, W., Jeromin, A., DeGray, B., Varshney, A., Sharma, Y., Szigeti-Buck, K., Ehrlich, B.E. J. Clin. Invest. (2006) [Pubmed]
  5. Acute changes in short-term plasticity at synapses with elevated levels of neuronal calcium sensor-1. Sippy, T., Cruz-Martín, A., Jeromin, A., Schweizer, F.E. Nat. Neurosci. (2003) [Pubmed]
  6. N-type Ca2+ channels are located on somata, dendrites, and a subpopulation of dendritic spines on live hippocampal pyramidal neurons. Mills, L.R., Niesen, C.E., So, A.P., Carlen, P.L., Spigelman, I., Jones, O.T. J. Neurosci. (1994) [Pubmed]
  7. Expression of the neuronal calcium sensor protein family in the rat brain. Paterlini, M., Revilla, V., Grant, A.L., Wisden, W. Neuroscience (2000) [Pubmed]
  8. Axonal transport of neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta in the adult rat sciatic nerve. Reynolds, A.J., Hendry, I.A., Bartlett, S.E. Neuroreport (2000) [Pubmed]
  9. Phosphatidylinositol 4-OH kinase is a downstream target of neuronal calcium sensor-1 in enhancing exocytosis in neuroendocrine cells. Rajebhosale, M., Greenwood, S., Vidugiriene, J., Jeromin, A., Hilfiker, S. J. Biol. Chem. (2003) [Pubmed]
  10. Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells. Koizumi, S., Rosa, P., Willars, G.B., Challiss, R.A., Taverna, E., Francolini, M., Bootman, M.D., Lipp, P., Inoue, K., Roder, J., Jeromin, A. J. Biol. Chem. (2002) [Pubmed]
  11. Neuronal Ca2+ sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin and PC12 cells and regulates neurosecretion from dense-core granules. McFerran, B.W., Graham, M.E., Burgoyne, R.D. J. Biol. Chem. (1998) [Pubmed]
  12. Neuronal Ca(2+) sensor 1. Characterization of the myristoylated protein, its cellular effects in permeabilized adrenal chromaffin cells, Ca(2+)-independent membrane association, and interaction with binding proteins, suggesting a role in rapid Ca(2+) signal transduction. McFerran, B.W., Weiss, J.L., Burgoyne, R.D. J. Biol. Chem. (1999) [Pubmed]
  13. Calcium-myristoyl switch, subcellular localization, and calcium-dependent translocation of the neuronal calcium sensor protein VILIP-3, and comparison with VILIP-1 in hippocampal neurons. Spilker, C., Braunewell, K.H. Mol. Cell. Neurosci. (2003) [Pubmed]
  14. Spatiotemporal distribution of neuronal calcium sensor-1 in the developing rat spinal cord. Kawasaki, T., Nishio, T., Kurosawa, H., Roder, J., Jeromin, A. J. Comp. Neurol. (2003) [Pubmed]
  15. Localization of neuronal calcium sensor-1 at the adult and developing rat neuromuscular junction. Garcia, N., Lanuza, M.A., Besalduch, N., Santafe, M.M., Jeromin, A., Tomas, J. J. Neurosci. Res. (2005) [Pubmed]
  16. N-terminal myristoylation regulates calcium-induced conformational changes in neuronal calcium sensor-1. Jeromin, A., Muralidhar, D., Parameswaran, M.N., Roder, J., Fairwell, T., Scarlata, S., Dowal, L., Mustafi, S.M., Chary, K.V., Sharma, Y. J. Biol. Chem. (2004) [Pubmed]
  17. Regulated expression of the neuronal calcium sensor-1 gene during long-term potentiation in the dentate gyrus in vivo. Génin, A., Davis, S., Meziane, H., Doyère, V., Jeromin, A., Roder, J., Mallet, J., Laroche, S. Neuroscience (2001) [Pubmed]
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