Reed R R, Bakalyar H A, Cunningham A M, Levy N S
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Soc Gen Physiol Ser. 1992;47:53-60.
Contributions from a wide spectrum of experimental systems have resulted in a dramatic increase in our understanding of this old and most enigmatic of the sensory systems. Many of the components of the odorant-induced transduction cascade have now been cloned, and the biochemistry, pharmacology, and regulatory mechanisms are being addressed in a logical fashion. One of the first priorities is to establish that the large family of putative receptor proteins described by Buck and Axel (1991) do, in fact, bind odorants. The ability to express members of this receptor family at high levels in the mammalian expression system is a first step in this direction. Determining specific ligand-receptor relationships is an extremely challenging task given the diversity of odorants able to be perceived and the potentially large size of the family of receptors. The role of other proteins in odorant presentation and processing, such as odorant binding protein produced in the lateral nasal gland (Pevsner et al., 1988), can be explored. A fascinating issue to be resolved is that of the distribution of receptor molecules within the population of olfactory sensory neurons. Does one cell express only one receptor, a small repertoire of receptors, or indeed the entire family? These questions can now be answered using a combined approach with in situ hybridization, immunocytochemistry, and single cell PCR techniques. One model of receptor distribution would provide for discrimination of a particular odorant by higher order analysis of the pattern of receptor neuron firing within the neuroepithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
来自广泛实验系统的贡献极大地增进了我们对这个古老且最神秘的感觉系统的理解。如今,气味诱导转导级联反应的许多组成部分已被克隆,其生物化学、药理学及调节机制正以合理的方式得到研究。首要任务之一是确定巴克和阿克塞尔(1991年)所描述的大量假定受体蛋白是否真的能结合气味分子。在哺乳动物表达系统中高水平表达该受体家族成员的能力是朝着这个方向迈出的第一步。鉴于可被感知的气味分子的多样性以及受体家族可能的庞大规模,确定特定的配体 - 受体关系是一项极具挑战性的任务。还可以探索其他蛋白质在气味呈现和处理中的作用,比如在侧鼻腺中产生的气味结合蛋白(佩夫斯纳等人,1988年)。一个有待解决的有趣问题是受体分子在嗅觉感觉神经元群体中的分布情况。一个细胞是只表达一种受体、一小部分受体,还是实际上表达整个家族的受体呢?现在可以通过原位杂交、免疫细胞化学和单细胞PCR技术相结合的方法来回答这些问题。一种受体分布模型将通过对神经上皮内受体神经元放电模式的高阶分析来实现对特定气味分子的辨别。(摘要截选至250词)