Gene Symbol: Ncs1
Description: neuronal calcium sensor 1
Alias: Freq, neuronal calcium sensor 1, NCS-1, frequenin-like protein, frequenin-like ubiquitous protein
Species: rat
Products:     Ncs1

Top Publications

  1. Gambino F, Pavlowsky A, Béglé A, Dupont J, Bahi N, Courjaret R, et al. IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation. Proc Natl Acad Sci U S A. 2007;104:9063-8 pubmed
    ..Because both proteins are highly expressed in neurons, these results suggest that IL1RAPL1-related mental retardation could result from a disruption of N-VGCC and/or NCS-1-dependent synaptic and neuronal activities. ..
  2. Nakamura T, Jeromin A, Smith G, Kurushima H, Koga H, Nakabeppu Y, et al. Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons. J Cell Biol. 2006;172:1081-91 pubmed
    ..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. ..
  3. Hui H, McHugh D, Hannan M, Zeng F, Xu S, Khan S, et al. Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth. J Physiol. 2006;572:165-72 pubmed
    ..The data suggest protein-protein interaction between NCS-1 and TRPC5, and involvement of this protein complex in retardation of neurite outgrowth. ..
  4. Sippy T, Cruz Martin A, Jeromin A, Schweizer F. Acute changes in short-term plasticity at synapses with elevated levels of neuronal calcium sensor-1. Nat Neurosci. 2003;6:1031-8 pubmed
    ..We conclude that separate mechanisms are responsible for determining basal synaptic strength and short-term plasticity. ..
  5. Koizumi S, Rosa P, Willars G, Challiss R, Taverna E, Francolini M, et al. Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells. J Biol Chem. 2002;277:30315-24 pubmed
    ..Taken together, NCS-1 enhances phosphoinositide turnover, resulting in enhancement of Ca2+ signaling and exocytosis. This is a novel regulatory mechanism of exocytosis that might involve the activation of phosphatidylinositol 4-kinase. ..
  6. Gohain D, Deka R, Tamuli R. Identification of critical amino acid residues and functional conservation of the Neurospora crassa and Rattus norvegicus orthologues of neuronal calcium sensor-1. Genetica. 2016;144:665-674 pubmed
    ..norvegicus NCS-1 was found conserved. Thus, we identified three critical amino acid residues of N. crassa NCS-1, and demonstrated its functional conservation across species using the orthologue from R. norvegicus. ..
  7. Drumond L, Mourão F, Leite H, Abreu R, Reis H, Moraes M, et al. Differential effects of swimming training on neuronal calcium sensor-1 expression in rat hippocampus/cortex and in object recognition memory tasks. Brain Res Bull. 2012;88:385-91 pubmed publisher
  8. Kapp Barnea Y, Melnikov S, Shefler I, Jeromin A, Sagi Eisenberg R. Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta regulate IgE receptor-triggered exocytosis in cultured mast cells. J Immunol. 2003;171:5320-7 pubmed
    ..We conclude that NCS-1 is involved in the control of regulated exocytosis in nonneural cells, where it contributes to stimulus-secretion coupling by interacting with PI4Kbeta and positive regulation of its activity. ..
  9. Schlecker C, Boehmerle W, Jeromin A, Degray B, Varshney A, Sharma Y, et al. Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium. J Clin Invest. 2006;116:1668-74 pubmed
    ..Lithium inhibited the enhancing effect of NCS-1 on InsP3R1 function, suggesting that InsP3R1/NCS-1 interaction is an essential component of the pathomechanism of bipolar disorder. ..

More Information


  1. McFerran B, Graham M, Burgoyne R. Neuronal Ca2+ sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin and PC12 cells and regulates neurosecretion from dense-core granules. J Biol Chem. 1998;273:22768-72 pubmed
    ..No effect of overexpression was seen on GH release because of Ca2+ in permeabilized cells suggesting that NCS-1 may have a regulatory but not direct role in neurosecretion. ..
  2. Rajebhosale M, Greenwood S, Vidugiriene J, Jeromin A, Hilfiker S. Phosphatidylinositol 4-OH kinase is a downstream target of neuronal calcium sensor-1 in enhancing exocytosis in neuroendocrine cells. J Biol Chem. 2003;278:6075-84 pubmed
    ..Taken together, the present data indicate that NCS-1 modulates the activity of PI4K, leading to increased levels of phosphoinositides and concomitant enhancement of exocytosis. ..
  3. Saab B, Georgiou J, Nath A, Lee F, Wang M, Michalon A, et al. NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory. Neuron. 2009;63:643-56 pubmed publisher
    ..Here we show that inducible, modest overexpression of neuronal calcium sensor 1 (Ncs1) selectively in the adult murine dentate gyrus (DG) promotes a specific form of exploratory ..
  4. Olafsson P, Soares H, Herzog K, Wang T, Morgan J, Lu B. The Ca2+ binding protein, frequenin is a nervous system-specific protein in mouse preferentially localized in neurites. Brain Res Mol Brain Res. 1997;44:73-82 pubmed
    ..The distribution and subcellular localization of Mfreq may help understand its cellular function. ..
  5. Kapp Barnea Y, Ninio Many L, Hirschberg K, Fukuda M, Jeromin A, Sagi Eisenberg R. Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta stimulate extracellular signal-regulated kinase 1/2 signaling by accelerating recycling through the endocytic recycling compartment. Mol Biol Cell. 2006;17:4130-41 pubmed
    ..Our results further identify the ERC as a crucial determinant in controlling ERK1/2 signaling. ..
  6. Chandra K, Sharma Y, Chary K. Characterization of low-energy excited states in the native state ensemble of non-myristoylated and myristoylated neuronal calcium sensor-1. Biochim Biophys Acta. 2011;1814:334-44 pubmed publisher
    ..Theoretical simulations reveal that these low-energy excited states are within an energy band of 2-4 kcal/mol with respect to the native state. ..
  7. Garcia N, Lanuza M, Besalduch N, Santafe M, Jeromin A, Tomas J. Localization of neuronal calcium sensor-1 at the adult and developing rat neuromuscular junction. J Neurosci Res. 2005;82:1-9 pubmed
    ..These results suggest that NCS-1 is involved in the formation and function of presynaptic nerve terminal part of the neuromuscular junction during synaptogenesis and in adult mammals. ..
  8. McFerran B, Weiss J, Burgoyne R. 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+). J Biol Chem. 1999;274:30258-65 pubmed
    ..This differs from the Ca(2+) myristoyl switch model for the closely related recoverin and suggests a possible action in rapid Ca(2+) signal transduction in response to local Ca(2+) signals. ..
  9. Haynes L, Fitzgerald D, Wareing B, O Callaghan D, Morgan A, Burgoyne R. Analysis of the interacting partners of the neuronal calcium-binding proteins L-CaBP1, hippocalcin, NCS-1 and neurocalcin delta. Proteomics. 2006;6:1822-32 pubmed
    ..These findings provide new clues to the functional roles of the neuronal calcium sensor proteins. ..
  10. Souza B, Torres K, Miranda D, Motta B, Caetano F, Rosa D, et al. Downregulation of the cAMP/PKA pathway in PC12 cells overexpressing NCS-1. Cell Mol Neurobiol. 2011;31:135-43 pubmed publisher
  11. Yip P, Wong L, Sears T, Yáñez Muñoz R, McMahon S. Cortical overexpression of neuronal calcium sensor-1 induces functional plasticity in spinal cord following unilateral pyramidal tract injury in rat. PLoS Biol. 2010;8:e1000399 pubmed publisher
    ..cortical neurons forming the corticospinal tract (CST) normally have low levels of the neuronal calcium sensor-1 (NCS1) protein...
  12. Comim C, Silva N, Mina F, Dominguini D, Scaini G, Morais M, et al. Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis. Synapse. 2014;68:474-9 pubmed publisher
  13. Zheng Q, Bobich J, Vidugiriene J, McFadden S, Thomas F, Roder J, et al. Neuronal calcium sensor-1 facilitates neuronal exocytosis through phosphatidylinositol 4-kinase. J Neurochem. 2005;92:442-51 pubmed
  14. Chen C, Yu L, Zhang P, Jiang J, Zhang Y, Chen X, et al. Human neuronal calcium sensor-1 shows the highest expression level in cerebral cortex. Neurosci Lett. 2002;319:67-70 pubmed
    ..Our results suggest that NCS-1 in human brain might be involved in a variety of brain functions such as sensory processing, motor control, emotional control, learning and memory. ..
  15. Pandalaneni S, Karuppiah V, Saleem M, Haynes L, Burgoyne R, Mayans O, et al. Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions. J Biol Chem. 2015;290:18744-56 pubmed publisher
    ..This appears to be driven by the variability of the conformation of the C-lobe-binding site, which has ramifications for the target specificity and diversity of NCS-1. ..
  16. McCue H, Haynes L, Burgoyne R. The diversity of calcium sensor proteins in the regulation of neuronal function. Cold Spring Harb Perspect Biol. 2010;2:a004085 pubmed publisher
    ..In this article, we summarize synaptotagmins in neurotransmitter release, the neuronal roles of calmodulin, and the functional significance of the NCS and the CaBP/calneuron protein families of neuronal Ca(2+) sensors. ..
  17. Lourenssen S, Jeromin A, Roder J, Blennerhassett M. Intestinal inflammation modulates expression of the synaptic vesicle protein neuronal calcium sensor-1. Am J Physiol Gastrointest Liver Physiol. 2002;282:G1097-104 pubmed
    The calcium-binding protein neuronal calcium sensor 1 (NCS-1) is involved in modulation of neurotransmitter release in the peripheral and central nervous systems...
  18. Brackmann M, Zhao C, Kuhl D, Manahan Vaughan D, Braunewell K. MGluRs regulate the expression of neuronal calcium sensor proteins NCS-1 and VILIP-1 and the immediate early gene arg3.1/arc in the hippocampus in vivo. Biochem Biophys Res Commun. 2004;322:1073-9 pubmed
    ..Therefore, mGluRs at concentrations which induce synaptic plasticity regulate the expression of IEGs and NCS proteins in different time frames and thus contribute to late phases of synaptic plasticity. ..
  19. Rosa D, Souza R, Souza B, Motta B, Caetano F, Jornada L, et al. NCS-1 expression in rat brain after electroconvulsive stimulation. Neurochem Res. 2007;32:81-5 pubmed
    ..The aim of this work was to analyze the expression of NCS-1 (neuronal calcium sensor 1, a protein that was found to be altered in post-mortem prefrontal cortex of schizophrenic patients) in ..
  20. Aravind P, Chandra K, Reddy P, Jeromin A, Chary K, Sharma Y. Regulatory and structural EF-hand motifs of neuronal calcium sensor-1: Mg 2+ modulates Ca 2+ binding, Ca 2+ -induced conformational changes, and equilibrium unfolding transitions. J Mol Biol. 2008;376:1100-15 pubmed publisher
    ..This study demonstrates the importance of Mg(2+) as a modulator of calcium homeostasis and active-state behavior of NCS-1. ..
  21. Guimarães M, Reis H, Guimarães L, Carneiro D, Ribeiro F, Gomez M, et al. Modulation of muscarinic signaling in PC12 cells overexpressing neuronal Ca2+ sensor-1 protein. Cell Mol Biol (Noisy-le-grand). 2009;55 Suppl:OL1138-50 pubmed
  22. Scalettar B, Rosa P, Taverna E, Francolini M, Tsuboi T, Terakawa S, et al. Neuronal calcium sensor-1 binds to regulated secretory organelles and functions in basal and stimulated exocytosis in PC12 cells. J Cell Sci. 2002;115:2399-412 pubmed
    ..These results also reveal interesting similarities and differences between transport organelles in differentiated neuroendocrine cells and neurons. ..
  23. de Castro E, Nef S, Fiumelli H, Lenz S, Kawamura S, Nef P. Regulation of rhodopsin phosphorylation by a family of neuronal calcium sensors. Biochem Biophys Res Commun. 1995;216:133-40 pubmed
    ..Together, our data suggest a general role for NCS proteins in the regulation of calcium-dependent phosphorylation in the nervous system. ..
  24. Ren X, Shand S, Takimoto K. Effective association of Kv channel-interacting proteins with Kv4 channel is mediated with their unique core peptide. J Biol Chem. 2003;278:43564-70 pubmed
    ..Because the three identified regions surround the large hydrophobic crevice based on the NCS-1 crystal structure, this crevice may be the association site of KChIPs for the channel protein. ..
  25. Bahi N, Friocourt G, Carrie A, Graham M, Weiss J, Chafey P, et al. IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis. Hum Mol Genet. 2003;12:1415-25 pubmed
    ..Taken together, our data suggest that IL1RAPL may regulate calcium-dependent exocytosis and provide insight into the understanding of physiopathological mechanisms underlying cognitive impairment resulting from IL1RAPL dysfunction. ..
  26. Kawasaki T, Nishio T, Kurosawa H, Roder J, Jeromin A. Spatiotemporal distribution of neuronal calcium sensor-1 in the developing rat spinal cord. J Comp Neurol. 2003;460:465-75 pubmed
    ..NCS-1 can serve as a Ca(2+)-sensor not only in neurons but also in radial glial cells or even in radially oriented astrocytes in the adult rat spinal cord. ..
  27. Taverna E, Francolini M, Jeromin A, Hilfiker S, Roder J, Rosa P. Neuronal calcium sensor 1 and phosphatidylinositol 4-OH kinase beta interact in neuronal cells and are translocated to membranes during nucleotide-evoked exocytosis. J Cell Sci. 2002;115:3909-22 pubmed
    b>Neuronal calcium sensor 1 (NCS-1) belongs to a family of EF-hand calcium-binding proteins and is mainly expressed in neurons and neuroendocrine cells, where it causes facilitation of neurotransmitter release through unknown mechanisms...
  28. de Barry J, Janoshazi A, Dupont J, Procksch O, Chasserot Golaz S, Jeromin A, et al. Functional implication of neuronal calcium sensor-1 and phosphoinositol 4-kinase-beta interaction in regulated exocytosis of PC12 cells. J Biol Chem. 2006;281:18098-111 pubmed
    ..PI4K-beta complex in regulated exocytosis. ..