A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.
A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.
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DOI：
10.1038/ncomms11866
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发表时间：
2016-06-15
影响因子：
16.6
通讯作者：
Benton R
中科院分区：
文献类型：
--
作者：
Gomez-Diaz C;Bargeton B;Abuin L;Bukar N;Reina JH;Bartoi T;Graf M;Ong H;Ulbrich MH;Masson JF;Benton R
CD 36跨膜蛋白在脂质摄取、细胞粘附和病原体感应中具有不同的作用。尽管有许多体外研究，但它们在天然细胞环境中的作用机制仍知之甚少。果蝇CD 36同源物，感觉神经元膜蛋白1（SNMP 1），以前被证明有利于检测的脂质来源的信息素，其同源受体在嗅觉纤毛。在这里，我们研究SNMP 1在体内的功能。结构-活性分析表明，SNMP 1的胞外域是必不可少的，但胞内和跨膜结构域，纤毛定位和信息素诱发的反应。SNMP 1可以被哺乳动物CD 36所取代，其胞外域可以与昆虫信息素相互作用。同源性建模，使用哺乳动物的LIMP-2结构作为模板，揭示了一个假定的隧道在SNMP 1胞外域是足够大，以容纳信息素分子。氨基酸取代预计将阻止这一隧道减少信息素的敏感性。我们提出了一个模型，其中SNMP 1漏斗从细胞外液的疏水性信息素的完整的膜受体。 CD 36相关的感觉神经元膜蛋白1（SNMP 1）有助于昆虫气味受体检测信息素。在这里，Gomez-Diaz等人表明SNMP 1胞外域对于功能是必不可少的，并提出它形成将信息素从细胞外液转运到其同源受体的通道。
CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia. Here we investigate how SNMP1 functions in vivo. Structure–activity dissection demonstrates that SNMP1's ectodomain is essential, but intracellular and transmembrane domains dispensable, for cilia localization and pheromone-evoked responses. SNMP1 can be substituted by mammalian CD36, whose ectodomain can interact with insect pheromones. Homology modelling, using the mammalian LIMP-2 structure as template, reveals a putative tunnel in the SNMP1 ectodomain that is sufficiently large to accommodate pheromone molecules. Amino-acid substitutions predicted to block this tunnel diminish pheromone sensitivity. We propose a model in which SNMP1 funnels hydrophobic pheromones from the extracellular fluid to integral membrane receptors. The CD36-related Sensory Neuron Membrane Protein 1 (SNMP1) facilitates pheromone detection by insect odorant receptors. Here Gomez-Diaz et al. show that the SNMP1 ectodomain is essential for function and propose that it forms a tunnel that transports pheromones from the extracellular fluid to their cognate receptors.