Ca2+ permeability of the channel pore is not essential for the delta2 glutamate receptor to regulate synaptic plasticity and motor coordination.
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.
Kakegawa
Wataru
W
Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Miyazaki
Taisuke
T
Hirai
Hirokazu
H
Motohashi
Junko
J
Mishina
Masayoshi
M
Watanabe
Masahiko
M
Yuzaki
Michisuke
M
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
D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; D005973:Glutamine; D002118:Calcium