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- Title
Functional Complementation of Glra1<sup>spd-ot</sup>, a Glycine Receptor Subunit Mutant, by Independently Expressed C-Terminal Domains.
- Authors
Villmann, Carmen; Oertel, Jana; Zhan-Lu Ma-Högemeier; Hollmann, Michael; Sprengel, Rolf; Becker, Kristina; Breitinger, Hans-Georg; Becker, Cord-Michael
- Abstract
The oscillator mouse (Glra1spd-ot) carries a 9bp microdeletion plus a 2bp microinsertion in the glycine receptorα1 subunit gene, resulting in the absence of functional α1 polypeptides from the CNS and lethality 3 weeks after birth. Depending on differential use of two splice acceptor sites in exon 9 of the Glra1 gene, the mutant allele encodes either a truncated α1 subunit (spdot-trc) or a polypeptide with a C-terminal missense sequence (spdot-elg). During recombinant expression, both splice variants fail to form ion channels. In complementation studies, a tail construct, encoding the deleted C-terminal sequence, was coexpressed with both mutants. Coexpression with spdot-trc produced glycine-gated ion channels. Rescue efficiency was increased by inclusion of the wild-type motif RRKRRH. In cultured spinal cord neurons from oscillator homozygotes, viral infection with recombinant C-terminal tail constructs resulted in appearance of endogenous α1 antigen. The functional rescue of α1 mutants by the C-terminal tail polypeptides argues for a modular subunit architecture of members of the Cys-loop receptor family.
- Subjects
GLYCINE; POLYPEPTIDES; ACTIVE biological transport; COMPLEMENTATION (Genetics); CENTRAL nervous system; MEDICAL research
- Publication
Journal of Neuroscience, 2008, p2440
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4400-08.2009