title: Ca2+ permeability of the channel pore is not essential for the delta2 glutamate receptor to regulate synaptic plasticity and motor coordination.
abstract: The delta2 glutamate receptor (GluRdelta2) plays a crucial role in cerebellar functions; mice with a disrupted GluRdelta2 gene (GluRdelta2-/-) display impaired synapse formation and abrogated long-term depression (LTD). However, the mechanisms by which GluRdelta2 functions have remained unclear. Because a GluRdelta2 mutation in lurcher mice causes channel activities characterized by Ca2+ permeability, GluRdelta2 was previously suggested to serve as a Ca2+-permeable channel in Purkinje cells. To test this hypothesis, we introduced a GluRdelta2 transgene, which had a mutation (Gln618Arg) in the putative channel pore, into GluRdelta2-/- mice. Interestingly, the mutant transgene rescued the major functional and morphological abnormalities of GluRdelta2-/- Purkinje cells, such as enhanced paired-pulse facilitation, impaired LTD at parallel fibre synapses, and sustained innervation by multiple climbing fibres. These results indicate that the conserved glutamine residue in the channel pore, which is crucial for all Ca2+-permeable glutamate receptors, is not essential for the function of GluRdelta2.
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.forename: Junko
authors.initials: J
authors.lastname: Motohashi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005973:Glutamine / Q000235:genetics; D036881:Long-Term Synaptic Depression / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D010641:Phenotype; D011689:Purkinje Cells / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D019076:Transgenes / Q000502:physiology
chemical_list: D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; D005973:Glutamine; D002118:Calcium