Nonet M L, Staunton J E, Kilgard M P, Fergestad T, Hartwieg E, Horvitz H R, Jorgensen E M, Meyer B J
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
J Neurosci. 1997 Nov 1;17(21):8061-73. doi: 10.1523/JNEUROSCI.17-21-08061.1997.
Rab molecules regulate vesicular trafficking in many different exocytic and endocytic transport pathways in eukaryotic cells. In neurons, rab3 has been proposed to play a crucial role in regulating synaptic vesicle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Similar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular electrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, suggesting that cholinergic transmission was generally depressed. Last, synaptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of normal levels, whereas in intersynaptic regions of the axon, vesicle populations were elevated. On the basis of the morphological defects at neuromuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near release sites.
Rab分子在真核细胞的许多不同的胞吐和胞吞运输途径中调节囊泡运输。在神经元中，有人提出rab3在调节突触小泡释放中起关键作用。为了阐明rab3在突触传递中的作用，我们分离并鉴定了秀丽隐杆线虫rab-3突变体。与小鼠rab3A突变体相似，这些突变体存活下来，仅表现出轻微的行为异常。与小鼠突变体不同的是，这些动物的突触传递受到了干扰。细胞外电生理记录显示，咽神经系统的突触传递受损。此外，rab-3动物对乙酰胆碱酯酶抑制剂涕灭威有抗性，这表明胆碱能传递普遍受到抑制。最后，rab-3突变体中的突触小泡群体发生了重新分布。在运动神经元中，突触处的小泡群体减少到正常水平的40%，而在轴突的突触间区域，小泡群体增加。基于神经肌肉接头处的形态学缺陷，我们推测RAB-3可能调节小泡向活性区的募集或释放位点附近小泡的隔离。
