Doc2alpha is an activity-dependent modulator of excitatory synaptic transmission.
Doc2alpha is a synaptic vesicle-associated Ca2 + -binding protein. To study the role of Doc2alpha in synaptic transmission and modulation, we generated homozygous null Doc2alpha mutant mice. In the CA1 region of hippocampal slices in the mutant mice, excitatory synaptic responses evoked with prolonged 5 Hz stimulation showed a significantly larger frequency facilitation followed by a steeper depression than those in wild-type mice, whereas there was no difference in synaptic transmission at lower frequencies or in paired-pulse facilitation. These results suggest that Doc2alpha regulates synaptic transmission when high Ca2 + concentrations in the presynaptic terminal are sustained. Furthermore, the mutant mice showed impairment in long-term potentiation and passive avoidance task. Thus, Doc2alpha may regulate transmitter release during repetitive synaptic activation, thereby contributing to memory formation.
Sakaguchi
G
G
Shionogi Institute for Medical Science, Settsu, Japan.
Manabe
T
T
Kobayashi
K
K
Orita
S
S
Sasaki
T
T
Naito
A
A
Maeda
M
M
Igarashi
H
H
Katsuura
G
G
Nishioka
H
H
Mizoguchi
A
A
Itohara
S
S
Takahashi
T
T
Takai
Y
Y
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D002478:Cells, Cultured; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018390:Gene Targeting; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
D002135:Calcium-Binding Proteins; C490418:Doc2a protein, mouse; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020033:Protein Isoforms; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione