Atypical membrane topology and heteromeric function of Drosophila odorant receptors in vivo.
Atypical membrane topology and heteromeric function of Drosophila odorant receptors in vivo.
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DOI：
10.1371/journal.pbio.0040020
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发表时间：
2006-02
期刊：
影响因子：
9.8
通讯作者：
Vosshall, Leslie B
中科院分区：
文献类型：
--
作者：
Benton, Richard;Sachse, Silke;Michnick, Stephen W;Vosshall, Leslie B
果蝇嗅觉感觉神经元（OSNs）表达两种气味受体（ORs）：一种是OR家族的不同成员，另一种是高度保守、广泛表达的受体OR83b。OR83b在体内对嗅觉至关重要，并在体外增强OR功能，但其作用的分子机制尚不清楚。在本研究中，我们发现OR83b在嗅觉信号转导发生的感觉纤毛中，与传统的ORs在早期的膜系统中异二聚，并将这些复合物偶联到保守的纤毛运输通路中，对于维持OR/OR83b复合物在感觉纤毛中的作用至关重要。OR/OR83b复合物对于促进通常只对二氧化碳有反应的感觉神经元中气味诱发信号的功能重建是必要和充分的。出乎意料的是，与所有已知的脊椎动物和线虫化学感觉受体不同，我们发现果蝇的ORs和OR83b采用了一种新颖的膜拓扑结构，其n端和细胞质中最保守的环。这些循环介导了ORs与OR83b的直接关联。我们的研究结果表明，OR83b是果蝇功能OR的普遍和不可分割的一部分。这种非典型异聚物和拓扑结构设计似乎是昆虫气味识别的特异性解决方案，使OR/OR83b复合物成为开发高选择性驱虫剂以破坏昆虫疾病媒介嗅觉介导的寻宿主行为的有吸引力的靶标。这项研究揭示了果蝇嗅觉受体的一种新的膜拓扑结构，并详细介绍了受体在感觉纤毛定位的分子机制。
Drosophila olfactory sensory neurons (OSNs) each express two odorant receptors (ORs): a divergent member of the OR family and the highly conserved, broadly expressed receptor OR83b. OR83b is essential for olfaction in vivo and enhances OR function in vitro, but the molecular mechanism by which it acts is unknown. Here we demonstrate that OR83b heterodimerizes with conventional ORs early in the endomembrane system in OSNs, couples these complexes to the conserved ciliary trafficking pathway, and is essential to maintain the OR/OR83b complex within the sensory cilia, where odor signal transduction occurs. The OR/OR83b complex is necessary and sufficient to promote functional reconstitution of odor-evoked signaling in sensory neurons that normally respond only to carbon dioxide. Unexpectedly, unlike all known vertebrate and nematode chemosensory receptors, we find that Drosophila ORs and OR83b adopt a novel membrane topology with their N-termini and the most conserved loops in the cytoplasm. These loops mediate direct association of ORs with OR83b. Our results reveal that OR83b is a universal and integral part of the functional OR in Drosophila. This atypical heteromeric and topological design appears to be an insect-specific solution for odor recognition, making the OR/OR83b complex an attractive target for the development of highly selective insect repellents to disrupt olfactory-mediated host-seeking behaviors of insect disease vectors. This study reveals a novel membrane topology for olfactory receptors in Drosophila and details the molecular mechanisms of receptor localization at the sensory cilia.