Jump to content

Neuronal calcium sensor-1

From Wikipedia, the free encyclopedia
(Redirected fromFrequenin)
NCS1
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesNCS1,FLUP, FREQ, neuronal calcium sensor 1
External IDsOMIM:603315;MGI:109166;HomoloGene:5719;GeneCards:NCS1;OMA:NCS1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

23413

14299

Ensembl

ENSG00000107130

ENSMUSG00000062661

UniProt

P62166

Q8BNY6

RefSeq (mRNA)

NM_014286
NM_001128826

NM_019681

RefSeq (protein)

NP_001122298
NP_055101

NP_062655

Location (UCSC)Chr 9: 130.17 – 130.24 MbChr 2: 31.14 – 31.19 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Neuronal calcium sensor-1(NCS-1) also known asfrequenin homolog (Drosophila)(freq) is aproteinthat is encoded by theFREQgenein humans.[5]NCS-1 is a member of theneuronal calcium sensorfamily,[6]a class ofEF handcontaining calcium-myristoyl-switch proteins.[7]

Function

[edit]

NCS-1 regulates synaptic transmission,[8]helps control the dynamics of nerve terminal growth,[9][10][8]is critical for some forms oflearningandmemoryinC. elegans[11]and mammals,[12]regulates corticohippocampalplasticity;and enhancing levels of NCS-1 in the mousedentate gyrusincreases spontaneous exploration of safe environments,[12]potentially linking NCS-1 tocuriosity.[13]

NCS-1 is a calcium sensor, not a calcium buffer (chelator); thus it is a high-affinity, low-capacity, calcium-binding protein.

Frq can substitute for calmodulin in some situations. It is thought to be associated with neuronal secretory vesicles and regulate neurosecretion.

  1. It is the Ca2+-sensing subunit of the yeast phosphatidylinositol (PtdIns)-4-OH kinase,PIK1
  2. It binds to many proteins, some in calcium dependent and some in calcium independent ways, and switches many of the targets "on" (some off).
    1. Calcineurin(protein phosphatase 2B)
    2. GRK2(G-protein-coupled receptor kinase 2)
    3. D2dopamine receptor
    4. IL1RAPL1(interleukin-1 receptor accessory protein-like 1 protein)
    5. PI4KIIIβ (type III phosphatidylinositol 4-kinase β)
    6. IP3 receptor(this activity is inhibited by lithium - a drug used for the treatment ofbipolar disorder)[14]
    7. 3',5'-cyclic nucleotidephosphodiesterases
    8. ARF1(ADPRibosylation factor 1)
    9. A type (Kv4.3;Shal-related subfamily, member 3)voltage-gated potassium channels
    10. Nitric oxide synthase
    11. TRPC5channel[15]
    12. Ric8a[16]
  3. Frq modulates Ca2+entry through a functional interaction with the α1voltage-gated Ca2+-channel subunit.[8]

Structure

[edit]

NCS-1 is a globular protein consisting of ten alpha-helices. Four pairs of alpha-helices each form independent 12-amino-acid loops containing a negatively charged calcium binding domain known as an EF-hand. However, only three of these EF hands are functional (the most N-terminal EF-hand does not bind calcium). They could be occupied not only by calcium but also by magnesium and zinc ions.[17]NCS-1 also contains at least two known protein binding domains, and a large surface exposed hydrophobic crevice containing EF-hands three and four. There is amyristoylationmotif at the N-terminus that presumably allows NCS-1 to associate withlipidmembranes.

Clinical significance

[edit]

The expression of NCS-1 increases inbipolar disorderand some forms ofschizophrenia[18]and decreases ininflammatory bowel disease.[19]NCS-1 has also been linked with Autism.[20]In addition NCS-1 is significant in intelligence in creating curiosity by its function on dopamine D2 receptors in the dentate gyrus, increasing memory for complex tasks.[21]

History

[edit]

NCS-1 was originally discovered inDrosophilaas a gain-of-function mutation associated with frequency-dependent increases inneurotransmission.[22]A role in neurotransmission was later confirmed inDrosophilausingfrqnull mutants.[8]Work in bovinechromaffin cellsdemonstrated that NCS-1 is also a modulator of neurotransmission in mammals.[23]The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the case.[24]

References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000107130–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000062661–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^Bourne Y, Dannenberg J, Pollmann V, Marchot P, Pongs O (April 2001)."Immunocytochemical localization and crystal structure of human frequenin (neuronal calcium sensor 1)".J. Biol. Chem.276(15): 11949–55.doi:10.1074/jbc.M009373200.PMID11092894.
  6. ^Burgoyne RD (2007)."Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling".Nat. Rev. Neurosci.8(3): 182–193.doi:10.1038/nrn2093.PMC1887812.PMID17311005.
  7. ^Burgoyne RD, O'Callaghan DW, Hasdemir B, Haynes LP, Tepikin AV (2004). "Neuronal Ca2+-sensor proteins: multitalented regulators of neuronal function".Trends Neurosci.27(4): 203–9.doi:10.1016/j.tins.2004.01.010.PMID15046879.S2CID24156457.
  8. ^abcdDason JS, Romero-Pozuelo J, Marin L, Iyengar BG, Klose MK, Ferrus A, Atwood HL (2009). "Frequenin/NCS-1 and the Ca2+-channel {alpha}1-subunit co-regulate synaptic transmission and nerve-terminal growth".Journal of Cell Science.122(22): 4109–4121.doi:10.1242/jcs.055095.PMID19861494.S2CID2663472.
  9. ^Romero-Pozuelo J, Dason JS, Atwood HL, Ferrus A (2007). "Chronic and acute alterations in the functional levels of Frequenins 1 and 2 reveal their roles in synaptic transmission and axon terminal morphology".European Journal of Neuroscience.26(9): 2428–2443.doi:10.1111/j.1460-9568.2007.05877.x.hdl:10261/72998.PMID17970740.S2CID11989516.
  10. ^Hui K, Fei GH, Saab BJ, Su J, Roder JC, Feng ZP (2007)."Neuronal calcium sensor-1 modulation of optimal calcium level for neurite outgrowth".Development.134(24): 4479–4489.doi:10.1242/dev.008979.PMID18039973.
  11. ^Gomez M, De Castro E, Guarin E, Sasakura H, Kuhara A, Mori I, Bartfai T, Bargmann CI, Nef P (2001)."Ca2+ signaling via the neuronal calcium sensor-1 regulates associative learning and memory in C. elegans".Neuron.30(1): 241–8.doi:10.1016/S0896-6273(01)00276-8.PMID11343658.S2CID9413106.
  12. ^abSaab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F, Mansuy IM, Roder JC (2009)."NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory".Neuron.63(5): 643–56.doi:10.1016/j.neuron.2009.08.014.PMID19755107.S2CID5321020.
  13. ^McDermott M (September 14, 2009)."Researchers discover the first-ever link between intelligence and curiosity".PHYS ORG.Retrieved21 September2012.
  14. ^Schlecker C, Boehmerle W, Jeromin A, DeGray B, Varshney A, Sharma Y, Szigeti-Buck K, Ehrlich BE (2006)."Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium".J. Clin. Invest.116(6): 1668–74.doi:10.1172/JCI22466.PMC1459068.PMID16691292.
  15. ^Hui H, McHugh D, Hannan M, Zeng F, Xu SZ, Khan SU, Levenson R, Beech DJ, Weiss JL (April 2006)."Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth".J. Physiol.572(Pt 1): 165–72.doi:10.1113/jphysiol.2005.102889.PMC1779652.PMID16469785.
  16. ^Romero-Pozuelo J, Dason JS, Mansilla A, Baños-Mateos S, Sardina JL, Chaves-Sanjuán A, Jurado-Gómez J, Santana E, Atwood HL, Hernández-Hernández A, Sánchez-Barrena MJ, Ferrús A (2014)."The guanine-exchange factor Ric8a binds to the Ca2+ sensor NCS-1 to regulate synapse number and neurotransmitter release".Journal of Cell Science.127(19): 4246–4259.doi:10.1242/jcs.152603.hdl:10261/167910.PMID25074811.
  17. ^Tsvetkov PO, Roman AY, Baksheeva VE, Nazipova AA, Shevelyova MP, Vladimirov VI, Buyanova MF, Zinchenko DV, Zamyatnin AA, Devred F, Golovin AV, Permyakov SE, Zernii EY (2018)."Functional Status of Neuronal Calcium Sensor-1 Is Modulated by Zinc Binding"(PDF).Frontiers in Molecular Neuroscience.11:459.doi:10.3389/fnmol.2018.00459.PMC6302015.PMID30618610.
  18. ^Koh PO, Undie AS, Kabbani N, Levenson R, Goldman-Rakic PS, Lidow MS (2003)."Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients".Proc Natl Acad Sci U S A.100(1): 313–7.Bibcode:2003PNAS..100..313K.doi:10.1073/pnas.232693499.PMC140961.PMID12496348.
  19. ^Lourenssen S, Jeromin A, Roder J, Blennerhassett MG (2002). "Intestinal inflammation modulates expression of the synaptic vesicle protein neuronal calcium sensor-1".Am. J. Physiol. Gastrointest. Liver Physiol.282(6): G1097–104.doi:10.1152/ajpgi.00320.2001.PMID12016136.S2CID42387548.
  20. ^Handley MT, Lian LY, Haynes LP, Burgoyne RD (2010)."Structural and functional deficits in a neuronal calcium sensor-1 mutant identified in a case of autistic spectrum disorder".PLOS ONE.5(5): e10534.Bibcode:2010PLoSO...510534H.doi:10.1371/journal.pone.0010534.PMC2866544.PMID20479890.
  21. ^McDermott M."Researchers discover the first-ever link between intelligence and curiosity".medicalxpress.com.Retrieved31 January2024.
  22. ^Pongs O, Lindemeier J, Zhu XR, Theil T, Engelkamp D, Krah-Jentgens I, Lambrecht HG, Koch KW, Schwemer J, Rivosecchi R, Mallart A, Galceran J, Canal I, Barbas A, Ferrus A (1993). "Frequenin--a novel calcium-binding protein that modulates synaptic efficacy in the Drosophila nervous system".Neuron.11(1): 15–28.doi:10.1016/0896-6273(93)90267-U.PMID8101711.S2CID30422835.
  23. ^McFerran BW, Weiss JL, Burgoyne RD (October 1999)."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".Journal of Biological Chemistry.274(42): 30258–65.doi:10.1074/jbc.274.42.30258.PMID10514519.
  24. ^Nef S, Fiumelli H, de Castro E, Raes MB, Nef P (1995). "Identification of neuronal calcium sensor (NCS-1) possibly involved in the regulation of receptor phosphorylation".J. Recept. Signal Transduct. Res.15(1–4): 365–78.doi:10.3109/10799899509045227.PMID8903951.

Further reading

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Neuronal_calcium_sensor-1&oldid=1201559291"