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  Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating

Saul, B., Kuner, T., Sobetzko, D., Brune, W., Hanefeld, F., Meinck, H., et al. (1999). Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. The Journal of Neuroscience, 19(3), 869-877. Retrieved from http://www.jneurosci.org/cgi/content/abstract/19/3/869.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-54B8-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-54BE-C
Genre: Journal Article

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JNeurosci_19_1999_869.pdf (Any fulltext), 247KB
 
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 Creators:
Saul, Brigitta, Author
Kuner, Thomas1, 2, 3, 4, 5, Author              
Sobetzko, Diana, Author
Brune, Wolfram, Author
Hanefeld, Folker, Author
Meinck, Hans−Michael, Author
Becker, Cord−Michael, Author
Affiliations:
1Interdisciplinary WIN-Research Group on Olfactory Dynamics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497717              
2Synaptic Transmission MNTB, Max Planck Institute for Medical Research, Max Planck Society, ou_1497745              
3Synaptic Transmission, Max Planck Institute for Medical Research, Max Planck Society, ou_1497744              
4Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
5Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: glycine; hyperekplexia; inhibition; receptor; startle disease; stiff baby syndrome
 Abstract: Missense mutations as well as a null allele of the human glycine receptor alpha1 subunit gene GLRA1 result in the neurological disorder hyperekplexia [startle disease, stiff baby syndrome, Mendelian Inheritance in Man (MIM) #149400]. In a pedigree showing dominant transmission of hyperekplexia, we identified a novel point mutation C1128A of GLRA1. This mutation encodes an amino acid substitution (P250T) in the cytoplasmic loop linking transmembrane regions M1 and M2 of the mature alpha1 polypeptide. After recombinant expression, homomeric alpha1(P250T) subunit channels showed a strong reduction of maximum whole-cell chloride currents and an altered desensitization, consistent with a prolonged recovery from desensitization. Apparent glycine binding was less affected, yielding an approximately fivefold increase in Ki values. Topological analysis predicts that the substitution of proline 250 leads to the loss of an angular polypeptide structure, thereby destabilizing open channel conformations. Thus, the novel GLRA1 mutant allele P250T defines an intracellular determinant of glycine receptor channel gating.

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Language(s): eng - English
 Dates: 1998-11-041998-05-251998-11-061999-02-011999-02-01
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
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 Rev. Type: Peer
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Title: The Journal of Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 19 (3) Sequence Number: - Start / End Page: 869 - 877 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187