The Lurcher mutation reveals Ca(2+) permeability and PKC modification of the GluRdelta channels.
The physiological function of the GluRdelta subfamily which is one of the glutamate receptor (GluR) channel subunits has not yet been clarified, because no GluR channel activity has been detected in heterologous expression systems. The Lurcher mutation, a point mutation of the GluRdelta2 subunit, converts it into a constitutively active and cation-permeating channel. We introduced this mutation into GluRdelta1 and GluRdelta2, AMPA-selective, and NMDA-selective GluR channel subunits, and characterized their channel properties. It was shown that the Lurcher mutation alters the gating properties of AMPA- and NMDA-selective GluR channels, but not their cation permeabilities nor metabolic modulations. These findings support the idea that the Lurcher mutant homomeric GluRdelta1 channels are permeable to Ca(2+) as do the mutant GluRdelta2 channels, reflecting their original channel properties. We also found that cation permeability of the mutant GluRdelta1 channels was decreased by TPA, a protein kinase C activator. It indicates the possibility that phosphorylation by PKC activation may inhibit channel with wild-type GluRdelta1 subunit.
Ikeno
K
K
Department of Cellular Neurobiology, Brain Research Institute, Niigata University, 1-Asahimachi-dori, Niigata 951-8585, Japan.
Yamakura
T
T
Yamazaki
M
M
Sakimura
K
K
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000235:genetics*; D002490:Central Nervous System / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
D002118:Calcium; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D008274:Magnesium; D011493:Protein Kinase C; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C108929:glutamate receptor delta 1; C107913:glutamate receptor delta 2; C104722:glutamate receptor ionotropic, AMPA 2