宾夕法尼亚大学医学院的研究人员利用一种新型的影像系统，观察一种与阿兹海默症及帕金森氏症沿着轴突恶化有关的重要蛋白质，轴突是神经细胞的延伸，将蛋白质带离细胞本体。
了解这个轴突运输的过程对于研究许多神经退化性疾病而言，是非常重要的。研究人员将焦点放在一组名为synuclein 和tau的运输蛋白质，这二种蛋白质分别与帕金森氏症和阿兹海默症有关。
有二种基本的运输蛋白质分别为快速组成及慢速组成蛋白质，其平均速度有200 到300倍的差异。
本研究的第一作者Subhojit Roy表示，直到现在为止，这些与疾病相关的蛋白质，其缓慢的运动机制仍然不明，因为它们的运输过程并未直接透过影像化观察。
Roy 构想出一种系统，可以同时在小鼠的轴途中，将两种经过标定的慢速组成-b 蛋白质在轴突中运输的过程影像化。这有助于厘清慢速蛋白质运输的特征。
结果研究人员发现，慢速蛋白质会一起运输，而且是快速地前进后，停留一段时间，再快速地前进，而不是整个过程都是缓慢的，研究结果也建议建议，快速和慢速蛋白质使用相同的基本机制运输。
(资料来源 : Bio.com)
英文原文链接:
原始出处:
The Journal of Neuroscience, March 21, 2007, 27(12):3131-3138; doi:10.1523/JNEUROSCI.4999-06.2007
Rapid and Intermittent Cotransport of Slow Component-b Proteins
Subhojit Roy,1,2 Matthew J. Winton,1 Mark M. Black,4 John Q. Trojanowski,1,2,3 and Virginia M.-Y. Lee1,2,3
1Center for Neurodegenerative Disease Research, 2Department of Pathology and Laboratory Medicine, and 3Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and 4Department of Anatomy and Cell Biology, Temple University Hospital, Philadelphia, Pennsylvania 19130
Correspondence should be addressed to Dr. Virginia M.-Y. Lee, Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Maloney Building, 3rd Floor, 3600 Spruce Street, Philadelphia, PA 19104. Email: vmylee@mail.med.upenn.edu
After synthesis in neuronal perikarya, proteins destined for synapses and other distant axonal sites are transported in three major groups that differ in average velocity and protein composition: fast component (FC), slow component-a (SCa), and slow component-b (SCb). The FC transports mainly vesicular cargoes at average rates of 200–400 mm/d. SCa transports microtubules and neurofilaments at average rates of 0.2–1 mm/d, whereas SCb translocates 200 diverse proteins critical for axonal growth, regeneration, and synaptic function at average rates of 2–8 mm/d. Several neurodegenerative diseases are characterized by abnormalities in one or more SCb proteins, but little is known about mechanisms underlying SCb compared with FC and SCa. Here, we use live-cell imaging to visualize and quantify the axonal transport of three SCb proteins, -synuclein, synapsin-I, and glyceraldehyde-3-phosphate dehydrogenase in cultured hippocampal neurons, and directly compare their transport to synaptophysin, a prototypical FC protein. All three SCb proteins move rapidly but infrequently with pauses during transit, unlike synaptophysin, which moves much more frequently and persistently. By simultaneously visualizing the transport of proteins at high temporal and spatial resolution, we show that the dynamics of -synuclein transport are distinct from those of synaptophysin but similar to other SCb proteins. Our observations of the cotransport of multiple SCb proteins in single axons suggest that they move as multiprotein complexes. These studies offer novel mechanistic insights into SCb and provide tools for further investigating its role in disease processes.
Key words: axonal transport; slow transport; slow component-b; -synuclein; synaptophysin; protein complexes
