Molecular Mechanism of selective transport for carotenoid in the silkworm, Bombyx mori

家蚕为某些类胡萝卜素通过血淋巴脂蛋白、脂蛋白从中肠腔到丝腺的组织特异性传递提供了非常明确的例子。脂蛋白含有叶黄素和β-胡萝卜素，是疏水核心中的一种复杂的脂类混合物。黄色(C)或肉色茧(F)突变体分别从脂蛋白中在丝腺中积累叶黄素或β-胡萝卜素。我们已经报道，C基因编码CD36基因家族成员Cameo2，该基因在丝腺中部作为叶黄素特异性转运体和跨膜非内在化脂蛋白受体发挥作用。利用GAL4-UAS双元表达系统进行定位克隆和转基因挽救实验，确定了F基因的性质。F基因编码SCRB15，这是与Cameo2类似的基因，氨基酸同源性为26%。SCRB15可能与β-胡萝卜素特异性非内化脂蛋白受体有关。在F突变体中，SCRB15没有表达，因为SCRB15的mRNA结构因编码外显子1.4kb的插入而严重中断。这个C和F基因都编码CD36同源基因的发现提出了一个问题，CD36同源蛋白如何识别类胡萝卜素种类的差异，从而允许从脂蛋白中摄取中间丝腺。我们认为分子机制是为了将特定的脂类从脂蛋白输送到靶组织。此外，跨膜脂蛋白受体和细胞内脂结合蛋白的功能协调也被提出，以实现从高密度脂蛋白到普通脂类的选择性细胞转运，如胆固醇酯和脂肪酸。因此，我们的数据也为脂质生物学中的这一一般机制提供了遗传学证据。

The silkworm, Bombyx mori provides very clear examples of tissue-specific delivery for certain carotenoid species from the midgut lumen to the silk gland via hemolymph lipoprotein, lipophorin. Lipophorin contains lutein and beta-carotene as a complex mixture of lipids in the hydrophobic core. The yellow(C) or flesh color cocoon(F) mutants accumulate lutein or beta-carotene in the middle silk gland from lipophorin, respectively. We have reported that the C gene encodes Cameo2, a member of CD36 gene family which has been known to function as as lutein specific transporter and transmembrane non-internalizing lipophorin receptor in the middle silk gland. The nature of the F gene was defined by positional cloning and transgenic rescue experiments with the binary GAL4-UAS expression system. The F gene encodes SCRB15, a paralog of Cameo2 with 26% amino acid identity. SCRB15 may be responsible for beta-carotene specific non-internalizing lipophorin receptor. In the F mutant, SCRB15 is not expressed because the mRNA structure of SCRB15 is severely disrupted due to a 1.4 kb insertion in a coding exon. This finding that both C and F genes encode CD36 homologs raises questions how CD36-homolog proteins recoginize the difference of carotenoid species which permits to uptake the middle silk gland from lipophorin.We believe the molecular machineries are for delivery of specific lipids from lipophorin to target tissues. Furthermore, functional coordination of transmembrane lipoprotein receptors and intracellular lipid-binding proteins has been proposed to achieve the selective cellular transport from HDL for general lipids, such as cholesteryl ester and fatty acids. Thus, our data also provide genetic evidence for this general mechanism in lipid biology.