Geppert M, Bolshakov V Y, Siegelbaum S A, Takei K, De Camilli P, Hammer R E, Südhof T C
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Nature. 1994 Jun 9;369(6480):493-7. doi: 10.1038/369493a0.
The small GTP-binding protein Rab3A is a Rab family member that is abundant in brain synaptic vesicles. Here we show that mice in which the rab3A gene has been mutated by homologous recombination do not express Rab3A but are viable and fertile. Electrophysiological recordings in hippocampal CA1 pyramidal cells indicate that most of their synaptic parameters are also normal, although synaptic depression after short trains of repetitive stimuli (15-30 stimuli at 14 Hz) is significantly increased. Levels of the Rab3A-binding protein rabphilin are decreased by 70%, but expression of more than 20 other synaptic proteins is unchanged. No compensatory changes were detected in other GTP-binding proteins or in proteins that interact with Rab3. Rab3A thus appears not to be essential for synaptic vesicle exocytosis but to play a role in the recruitment of synaptic vesicles for exocytosis during repetitive stimulation.
小GTP结合蛋白Rab3A是Rab家族的一员，在脑突触小泡中含量丰富。我们在此表明，通过同源重组使rab3A基因发生突变的小鼠不表达Rab3A，但仍可存活且能生育。海马CA1锥体细胞的电生理记录表明，尽管短串重复刺激（14 Hz下15 - 30次刺激）后的突触抑制显著增加，但其大多数突触参数仍正常。Rab3A结合蛋白rabphilin的水平降低了70%，但其他20多种突触蛋白的表达未发生变化。在其他GTP结合蛋白或与Rab3相互作用的蛋白中未检测到代偿性变化。因此，Rab3A似乎对突触小泡胞吐作用并非必不可少，但在重复刺激期间参与募集用于胞吐的突触小泡。
