Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Quick Search
My eDoc
Session History
Support Wiki
Direct access to
document ID:

          Institute: MPI für medizinische Forschung     Collection: Abteilung Zellphysiologie     Display Documents

ID: 22663.0, MPI für medizinische Forschung / Abteilung Zellphysiologie
Novel GLRA1 Missense Mutation (P250T) in Dominant Hyperekplexia Defines an Intracellular Determinant of Glycine Receptor Channel Gating
Translation of Title:Novel GLRA1 Missense Mutation (P250T) in Dominant Hyperekplexia Defines an Intracellular Determinant of Glycine Receptor Channel Gating
Authors:Saul, Brigitta; Kuner, Thomas; Sobetzko, Diana; Brune, Wolfram; Hanefeld, Folker; Meinck, Hans-Michael; Becker, Cord-Michael
Date of Publication (YYYY-MM-DD):1999-02
Title of Journal:Journal of Neuroscience
Journal Abbrev.:J. Neurosci.
Issue / Number:3
Start Page:869
End Page:877
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Missense mutations as well as a null allele of the human glycine receptor alpha 1 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 alpha 1 polypeptide. After recombinant expression, homomeric alpha 1P250T 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.
Free Keywords:glycine; hyperekplexia; inhibition; receptor; startle disease; stiff baby syndrome
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Zellphysiologie/
Identifiers:URI:http://www.jneurosci.org/cgi/content/full/19/3/869 [Full text]
URI:http://www.jneurosci.org/cgi/content/abstract/19/3... [Abstract]
URI:http://www.jneurosci.org/cgi/reprint/19/3/869 [Fulltext PDF]
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.