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ATCAY  -  ataxia, cerebellar, Cayman type

Homo sapiens

Synonyms: Ataxia cayman type protein, BNIP-2-homology, BNIP-H, CLAC, Caytaxin, ...
 
 
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Disease relevance of ATCAY

 

Psychiatry related information on ATCAY

 

High impact information on ATCAY

  • Three-dimensional protein structural modeling predicts that the caytaxin ligand is more polar than vitamin E. Identification of the caytaxin ligand may help develop a therapy for Cayman ataxia [4].
  • The extracellular domain of CLAC-P/collagen type XXV was secreted by furin convertase, and the N-terminus of CLAC deposited in AD brains was pyroglutamate modified [5].
  • CLAC displays features characteristic of a collagen protein, e.g. it forms a partly protease-resistant triple-helical structure, exhibits an intermediate affinity for heparin, and is glycosylated [6].
  • Mostly separate distributions of CLAC- versus Abeta40- or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of beta-amyloid deposits [1].
  • In DS cerebral cortex, diffuse plaques in young patients were negative for CLAC, whereas a subset of SP became CLAC-positive in patients aged 35 to 50 years, before the appearance of Abeta40 [1].
 

Biological context of ATCAY

  • To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates [7].
  • The above data, disease phenotypes, and mutant animals suggest that Caytaxin may be essential for synaptic function [8].
  • In 300-day-old animals beta 1-adrenoceptors accounted for 83% (CLAC) and 68% (BIO) of total beta-adrenoceptor binding sites, whereas only 26% (CLAC) and 6% (BIO) of the isoprenaline effect on cAMP formation were mediated via beta 1-adrenoceptors [9].
  • In the background of previous biochemical, behavioral and electrophysiological studies in the dt rat, our data are compatible with a vital role for caytaxin in the development and neurophysiology of cerebellar cortex [10].
 

Anatomical context of ATCAY

  • In AD and DS cerebral cortex, CLAC invariably colocalized with Abeta42 but often lacked Abeta40- or thioflavin S (thioS)-reactivities [1].
  • Immunohistochemistry and in situ hybridisation revealed high BNIP-H expression in hippocampus and cerebellum, broadly overlapping with the expression pattern previously reported for KGA [2].
  • Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to neurite terminals and reduces glutamate levels [2].
  • Caytaxin deficiency disrupts signaling pathways in cerebellar cortex [7].
  • Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input [7].
 

Associations of ATCAY with chemical compounds

  • These results strongly suggest that through binding to KGA, BNIP-H could regulate glutamate synthesis at synapses during neurotransmission [2].
  • Glutaraldehyde cross-linked ENA5His crystals (CLAC) packed in a column separated pure enantiomers from the racemic mixture of the drug [11].
  • Importantly, the frequently used thioflavin T-binding assay failed to reveal these effects of CLAC [12].
 

Analytical, diagnostic and therapeutic context of ATCAY

References

  1. Mostly separate distributions of CLAC- versus Abeta40- or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of beta-amyloid deposits. Kowa, H., Sakakura, T., Matsuura, Y., Wakabayashi, T., Mann, D.M., Duff, K., Tsuji, S., Hashimoto, T., Iwatsubo, T. Am. J. Pathol. (2004) [Pubmed]
  2. Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to neurite terminals and reduces glutamate levels. Buschdorf, J.P., Li Chew, L., Zhang, B., Cao, Q., Liang, F.Y., Liou, Y.C., Zhou, Y.T., Low, B.C. J. Cell. Sci. (2006) [Pubmed]
  3. CLAC binds to amyloid beta peptides through the positively charged amino acid cluster within the collagenous domain 1 and inhibits formation of amyloid fibrils. Osada, Y., Hashimoto, T., Nishimura, A., Matsuo, Y., Wakabayashi, T., Iwatsubo, T. J. Biol. Chem. (2005) [Pubmed]
  4. Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse. Bomar, J.M., Benke, P.J., Slattery, E.L., Puttagunta, R., Taylor, L.P., Seong, E., Nystuen, A., Chen, W., Albin, R.L., Patel, P.D., Kittles, R.A., Sheffield, V.C., Burmeister, M. Nat. Genet. (2003) [Pubmed]
  5. CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV. Hashimoto, T., Wakabayashi, T., Watanabe, A., Kowa, H., Hosoda, R., Nakamura, A., Kanazawa, I., Arai, T., Takio, K., Mann, D.M., Iwatsubo, T. EMBO J. (2002) [Pubmed]
  6. Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. Söderberg, L., Kakuyama, H., Möller, A., Ito, A., Winblad, B., Tjernberg, L.O., Näslund, J. J. Biol. Chem. (2005) [Pubmed]
  7. Caytaxin deficiency disrupts signaling pathways in cerebellar cortex. Xiao, J., Gong, S., Ledoux, M.S. Neuroscience (2007) [Pubmed]
  8. Expression and localization of Cayman ataxia-related protein, Caytaxin, is regulated in a developmental- and spatial-dependent manner. Hayakawa, Y., Itoh, M., Yamada, A., Mitsuda, T., Nakagawa, T. Brain Res. (2007) [Pubmed]
  9. Efficiency of beta-adrenoceptor subtype coupling to cardiac adenylyl cyclase in cardiomyopathic and control hamsters. Witte, K., Schnecko, A., Olbrich, H.G., Lemmer, B. Eur. J. Pharmacol. (1995) [Pubmed]
  10. Caytaxin deficiency causes generalized dystonia in rats. Xiao, J., Ledoux, M.S. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  11. Enantioselective affinity chromatography of a chiral drug by crystalline and carrier-bound antibody fab fragment. Vuolanto, A., Leisola, M., Jokela, J. Biotechnol. Prog. (2004) [Pubmed]
  12. Collagenous Alzheimer amyloid plaque component assembles amyloid fibrils into protease resistant aggregates. Söderberg, L., Dahlqvist, C., Kakuyama, H., Thyberg, J., Ito, A., Winblad, B., Näslund, J., Tjernberg, L.O. FEBS J. (2005) [Pubmed]
  13. CLAC binds to aggregated Abeta and Abeta fragments, and attenuates fibril elongation. Kakuyama, H., Söderberg, L., Horigome, K., Winblad, B., Dahlqvist, C., Näslund, J., Tjernberg, L.O. Biochemistry (2005) [Pubmed]
 
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