Gilbert S P, Sloboda R D
J Cell Biol. 1984 Aug;99(2):445-52. doi: 10.1083/jcb.99.2.445.
A reconstituted model was devised to study the mechanisms of fast axonal transport in the squid Loligo pealei. Axonal vesicles were isolated from axoplasm of the giant axon and labeled with rhodamine-conjugated octadecanol, a membrane-specific fluorescent probe. The labeled vesicles were then injected into a fresh preparation of extruded axoplasm in which endogenous vesicle transport was occurring normally. The movement of the fluorescent, exogenous vesicles was observed by epifluorescence microscopy for as long as 5 min without significant photobleaching, and the transport of endogenous, nonfluorescent vesicles was monitored by video-enhanced differential interference-contrast microscopy. The transport of fluorescent, exogenous vesicles was shown to be bidirectional and ATP-dependent and occurred at a mean rate of 6.98 +/- 4.11 micron/s (mean +/- standard deviation, n = 41). In comparison, the mean rate of transport of nonfluorescent, endogenous vesicles in control axoplasm treated with vesicle buffer alone was 4.76 +/- 1.60 micron/s (n = 64). These rates are slightly higher than the mean rate of endogenous vesicle movement in extruded axoplasm (3.56 +/- 1.05 micron/s, n = 40) not subject to vesicles or vesicle buffer. Not all vesicles and organelles, exogenous or endogenous, were observed to move. In experiments in which proteins of the surface of the fluorescent vesicles were digested with trypsin before injection, no movement of the fluorescent vesicles was observed, although the transport of endogenous vesicles and organelles appeared to proceed normally. The results summarized above indicate that isolated vesicles, incorporated into axoplasm, move with the characteristics of fast axonal transport. Because the vesicles are fluorescent, they can be readily distinguished from nonfluorescent, endogenous vesicles. Moreover, this system permits vesicle characteristics to be experimentally manipulated, and therefore may prove valuable for the elucidation of the mechanisms of fast axonal transport.
设计了一种重构模型来研究枪乌贼(Loligo pealei)轴突快速运输的机制。从巨大轴突的轴浆中分离出轴突囊泡,并用罗丹明偶联的十八烷醇(一种膜特异性荧光探针)进行标记。然后将标记的囊泡注射到新鲜制备的已挤出轴浆中,其中内源性囊泡运输正常发生。通过落射荧光显微镜观察荧光外源性囊泡的运动长达5分钟,且无明显光漂白现象,并通过视频增强微分干涉对比显微镜监测内源性非荧光囊泡的运输。结果表明,荧光外源性囊泡的运输是双向的且依赖ATP,平均运输速率为6.98±4.11微米/秒(平均值±标准差,n = 41)。相比之下,仅用囊泡缓冲液处理的对照轴浆中非荧光内源性囊泡的平均运输速率为4.76±1.60微米/秒(n = 64)。这些速率略高于未接触囊泡或囊泡缓冲液的挤出轴浆中内源性囊泡运动的平均速率(3.56±1.05微米/秒,n = 40)。并非所有外源性或内源性的囊泡和细胞器都能观察到移动。在注射前用胰蛋白酶消化荧光囊泡表面蛋白质的实验中,未观察到荧光囊泡移动,尽管内源性囊泡和细胞器的运输似乎正常进行。上述结果表明,掺入轴浆中的分离囊泡具有轴突快速运输的特征。由于囊泡是荧光的,它们可以很容易地与非荧光内源性囊泡区分开来。此外,该系统允许对囊泡特性进行实验操作,因此可能对阐明轴突快速运输的机制具有重要价值。