Role of rab GDP dissociation inhibitor alpha in regulating plasticity of hippocampal neurotransmission.
Rab GDP dissociation inhibitor alpha (Rab GDIalpha) is a regulator of the Rab small G proteins implicated in neurotransmission, and mutations of Rab GDIalpha cause human X-linked mental retardation associated with epileptic seizures. In Rab GDIalpha-deficient mice, synaptic potentials in the CA1 region of the hippocampus displayed larger enhancement during repetitive stimulation, which was apparently opposite to the phenotype of Rab3A-deficient mice. Furthermore, the Rab GDIalpha-deficient mice showed hypersensitivity to bicuculline, an inducer of epileptic seizures. These results suggest that Rab GDIalpha plays a specialized role in Rab3A recycling to suppress hyperexcitability via modulation of presynaptic forms of plasticity.
Ishizaki
H
H
Takai Biotimer Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, c/o JCR Pharmaceuticals, Kobe 651-2241, Japan.
Miyoshi
J
J
Kamiya
H
H
Togawa
A
A
Tanaka
M
M
Sasaki
T
T
Endo
K
K
Mizoguchi
A
A
Ozawa
S
S
Takai
Y
Y
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced; D013347:Subcellular Fractions / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
D017931:DNA Primers; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D020692:rab3 GTP-Binding Proteins