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图释2004年诺贝尔医学奖
瑞典皇家科学院诺贝尔奖委员会刚刚公布了2004年度诺贝尔生理学或医学奖获奖人选：美国科学家理查德-阿克塞尔和琳达-巴克，以表彰两人在气味受体和嗅觉系统组织方式研究中作出的贡献。理查德-阿克塞尔在哥伦比亚大学戈瓦尔德-休格医学院和哈梅尔医学中心工作。琳达-巴克是华盛顿州西雅图市弗雷德-哈钦松癌症研究所工作人员(女)，今年奖金为100万美元
理查德-阿克塞尔：
screen.width-333)this.width=screen.width-333" width=300 height=324 title="Click to view full richiad.jpg (300 X 324)" border=0 align=absmiddle> 琳达-巴克
screen.width-333)this.width=screen.width-333" width=450 height=338 title="Click to view full 女.jpg (450 X 338)" border=0 align=absmiddle> 人类的嗅觉长期以来一直是一个非常神秘的领域。人类认识和记忆1万种不同气味的基本原理一直不为人所知。今年诺贝尔医学奖或生理学奖的获奖者解决了这一问题。他们所进行的一系列先驱性的研究向我们清楚地阐释了我们的嗅觉系统是如何运作的。
1 嗅觉是怎样产生的？
Odor molecules entering the nose are thought to be recognized by receptors found in cilia of olfactory neurons. Neurons with specific receptors are arranged randomly within zones in the olfactory lining of the nasal cavity. Signals from neurons with the same receptors converge on structures called glomeruli in the olfactory bulb. The pattern of activity in these glomeruli creates a pattern or code that the brain may interpret as different odors. The information is carried by nerve fibers to many brain regions, where it affects thoughts, emotions, and behavior
嗅觉系统大概图.bmp (273.24k) 再贴一张嗅觉系统
screen.width-333)this.width=screen.width-333" width=521 height=316 title="Click to view full 嗅觉系统.jpg (521 X 316)" border=0 align=absmiddle> 理查德•阿克塞尔和琳达•巴克1991年联合发表了他们有关嗅觉的基础论文。他们在论文中形容了嗅觉受体的一千种基因组成的基因家族。他们随后独立地展开工作。他们进一步通过分子结构和细胞组织清楚地向我们阐述了嗅觉系统。 理查德•阿克塞尔和琳达•巴克得出的结论认为每个嗅觉受体细胞都只表达某一种特定气味受体基因。这个结论出乎人们的意料。
2 什么是嗅觉受体（Odorant receptors）呢
It appears that there may be hundreds of odorant receptors, but only one (or at most a few) expressed in each olfactory receptor neuron. A large family of odorant receptors was cloned in 1991 by Linda Buck and Richard Axel (Buck and Axel, 1991) and the mRNA encoding these proteins has been found in olfactory tissue. These families may be encoded by as many as 1000 different genes. This is a huge amount and accounts for about 2% of the human genome. In humans, however, most are inactive pseudogenes and only around 350 code for functional receptors. There are many more functional genes in macrosmatic animals like rats. These receptor proteins are members of a well known receptor family called the 7-transmembrane domain G-protein coupled receptors (GPCRs - see Fig. below). The hydrophobic regions (the transmembrane parts) contain maximum sequence homology to other members of the G-protein linked receptor family. There are some notable features of these olfactory receptors, like the divergence in sequence in the 3rd, 4th and 5th transmembrane domains, that suggest a how a large number of different odorants may be discriminated
screen.width-333)this.width=screen.width-333" width=344 height=254 title="Click to view full 受体1.jpg (344 X 254)" border=0 align=absmiddle> 三、神经元Odorant receptor neurons (ORNs)
图搞颠倒了，见上图，^_^
The receptor cells are bipolar neurones in the nasal epithelium (see figure "Olfactory Receptor Neuron" above). It is thought that each ORN expresses only one type of receptor (out of the total of about 350). The ORNs are unique to the extent that they are capable of regenerating. They possess cilia which project into the mucus (these contain the receptor proteins) and, at the other end, axons that project to the olfactory bulb. 10-100 axons form up into bundles that penetrate the ethmoidal cribriform plate and terminate in the olfactory bulb, converging on synaptic glomeruli. ORNs expressing the same receptor protein synapse onto the same glomerulus in the olfactory bulb. There are two olfactory bulbs, one in each nasal cavity. In humans there are about 6M receptor cells in each nostril and this rises to 50M olfactory receptor neurons in the rat. The diagram below shows the incoming axons from ORNs (in green) synapsing with glomeruli in the olfactory bulb.
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作者:admin@医学,生命科学 2011-02-13 17:11
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