Titre
Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating.
Type
article
Institution
Externe
Périodique
Auteur(s)
Saul, B.
Auteure/Auteur
Kuner, T.
Auteure/Auteur
Sobetzko, D.
Auteure/Auteur
Brune, W.
Auteure/Auteur
Hanefeld, F.
Auteure/Auteur
Meinck, H.M.
Auteure/Auteur
Becker, C.M.
Auteure/Auteur
Liens vers les personnes
ISSN
0270-6474
Statut éditorial
Publié
Date de publication
1999
Volume
19
Numéro
3
Première page
869
Dernière page/numéro d’article
877
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
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.
Sujets
PID Serval
serval:BIB_7512A3B970DC
PMID
Date de création
2010-03-29T11:14:15.407Z
Date de création dans IRIS
2025-05-20T23:06:05Z
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Nom
BIB_7512A3B970DC.P001.pdf
Version du manuscrit
preprint
Taille
246.14 KB
Format
Adobe PDF
PID Serval
serval:BIB_7512A3B970DC.P001
Somme de contrôle
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