PubMed 19244519

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.1 , Kir6.2

Title: Functional complementation of Glra1(spd-ot), a glycine receptor subunit mutant, by independently expressed C-terminal domains.

Authors: Carmen Villmann, Jana Oertel, Zhan-Lu Ma-Högemeier, Michael Hollmann, Rolf Sprengel, Kristina Becker, Hans-Georg Breitinger, Cord-Michael Becker

Journal, date & volume: J. Neurosci., 2009 Feb 25 , 29, 2440-52

PubMed link:

The oscillator mouse (Glra1(spd-ot)) carries a 9 bp microdeletion plus a 2 bp microinsertion in the glycine receptor alpha1 subunit gene, resulting in the absence of functional alpha1 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 alpha1 subunit (spd(ot)-trc) or a polypeptide with a C-terminal missense sequence (spd(ot)-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 spd(ot)-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 alpha1 antigen. The functional rescue of alpha1 mutants by the C-terminal tail polypeptides argues for a modular subunit architecture of members of the Cys-loop receptor family.