title: The C-terminal domain of glutamate receptor subunit 1 is a target for calpain-mediated proteolysis.
abstract: The AMPA receptors are glutamate-gated ion channels mediating synaptic transmission at the majority of excitatory synapses in the mammalian CNS. They are composed of four subunits (GluR1-4) which exist in two alternatively spliced variants (flip and flop) and are generally considered to form pentameric receptors. The transmembrane structure of the receptors remains a matter of controversy as some data suggest a transmembrane topology consisting of five, four, or three membrane spanning regions. Some receptor properties have been shown to be regulated by phosphorylation processes as well as by the phospholipid environment. More recently, we have shown that calcium treatment of thin (10 microns) frozen-thawed brain sections resulted in profound modifications of the immunochemical properties of the AMPA receptors. More specifically, immunolabelling of the AMPA receptors with antibodies directed against the C-terminal domain of GluR1 and GluR2/3 was markedly decreased in dendritic fields following such treatment at 35 degrees C. This effect was temperature-dependent and completely blocked by inhibitors of the calcium-dependent proteases calpains, and we suggested that calpains are involved in the regulation of AMPA receptor properties. The results of the present study demonstrate that calpain activation produces a partial proteolysis in the C-terminal domain of the receptors and generates a new receptor species with an apparent molecular weight of 103,000 mol. wt. Sequence analysis of the GluR1 C-terminal domain suggests a couple of cleavage sites for calpains. These results are of particular interest considering the body of evidence implicating calpains and changes in excitatory amino acid receptors in mechanisms of synaptic plasticity as well as in neurodegenerative processes.
authors.affiliation: Neuroscience Program, USC, Los Angeles 90089-2520, USA.
authors.forename: X
authors.initials: X
authors.lastname: Bi
authors.forename: V
authors.initials: V
authors.lastname: Chang
authors.forename: E
authors.initials: E
authors.lastname: Molnar
authors.forename: R A
authors.initials: RA
authors.lastname: McIlhinney
authors.forename: M
authors.initials: M
authors.lastname: Baudry
mesh_terms: D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology*; D007150:Immunohistochemistry; D010447:Peptide Hydrolases / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism*; D013696:Temperature
chemical_list: D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D010447:Peptide Hydrolases; D002154:Calpain; D002118:Calcium