New role of delta2-glutamate receptors in AMPA receptor trafficking and cerebellar function.
Previous gene knockout studies have shown that the orphan glutamate receptor delta2 (GluRdelta2) is critically involved in synaptogenesis between parallel fibers and Purkinje cells during development. However, the precise function of GluRdelta2 and whether it is functional in the mature cerebellum remain unclear. To address these issues, we developed an antibody specific for the putative ligand-binding region of GluRdelta2, and application of this antibody to cultured Purkinje cells induced AMPA receptor endocytosis, attenuated synaptic transmission and abrogated long-term depression. Moreover, injection of this antibody into the subarachnoidal supracerebellar space of adult mice caused transient cerebellar dysfunction, such as ataxic gait and poor performance in the rotorod test. These results indicate that GluRdelta2 is involved in AMPA receptor trafficking and cerebellar function in adult mice.
Hirai
Hirokazu
H
Laboratory for Memory & Learning, RIKEN Brain Science Institute, Saitama 351-0198, Japan. hirai@med.kobe-u.ac.jp
Launey
Thomas
T
Mikawa
Sumiko
S
Torashima
Takashi
T
Yanagihara
Dai
D
Kasaura
Tsuyoshi
T
Miyamoto
Akihiro
A
Yuzaki
Michisuke
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D004705:Endocytosis / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport; D011689:Purkinje Cells / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000276:immunology / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D000906:Antibodies; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2