C-terminal truncation affects kinetic properties of GluR1 receptors.
GluR1flop receptors in which the C-terminal 52 amino acids had been recombinantly removed were characterized with whole-cell recording and binding assays. Compared to wildtype GluR1, truncated receptors showed faster desensitization and deactivation and they recovered more slowly from desensitization. The EC50 for glutamate was increased 2-fold. In binding tests, K(D)s for [3H]fluorowillardiine were 1.5 times larger for truncated receptors. According to receptor simulations, most differences can be explained if the C-terminal domain is assumed to stabilize the ligand-bound closed and open states. The effects on response waveforms are different from those caused by phosphorylation, suggesting that the C-terminus influences receptor function in multiple ways. Truncated forms of GluR1 identical or similar to the one examined here may also be generated by calcium-activated proteases during intense synaptic activity. The lowered affinity and faster inactivation of these receptors suggests that their presence does not represent a risk for neuronal viability.
Suzuki
Erika
E
Department of Pharmacology, Southern Illinois University School of Medicine, MC 9629, 801 N. Rutledge, Room 3275, Springfield, IL 62702, USA.
Kessler
Markus
M
Arai
Amy C
AC
D000595:Amino Acid Sequence; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology; D001581:Benzothiadiazines / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D004232:Diuretics / Q000378:metabolism / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000166:cytology; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D001569:Benzodiazepines; D001581:Benzothiadiazines; D004232:Diuretics; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D008024:Ligands; D018091:Receptors, AMPA; C061950:GYKI 52466; C004639:cyclothiazide