Development of the Swimbladder Surfactant System and Biogenesis of Lysosome-Related Organelles Is Regulated by BLOS1 in Zebrafish
Development of the Swimbladder Surfactant System and Biogenesis of Lysosome-Related Organelles Is Regulated by BLOS1 in Zebrafish
复制标题
斑马鱼游泳鳔表面活性剂系统的发育和溶酶体相关细胞器的生物发生受 BLOS1 调节。
DOI：
10.1534/genetics.117.300621
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发表时间：
2018-03-01
期刊：
影响因子：
3.3
通讯作者：
Huang, Kaiyao
中科院分区：
文献类型：
--
作者：
Chen, Tianbing;Song, Guili;Huang, Kaiyao
Hermansky-Pudlak综合征(HPS)是一种常染色体隐性遗传病，以眼皮肤白化和溶酶体相关细胞器(LRO)生物发生缺陷引起的血小板储存池缺陷为特征。到目前为止，已鉴定出10个HPS基因，其中3个属于八聚体复合体BLOC-1(溶酶体相关细胞器复合体的生物发生1)。BLOC-1复合体的一个亚基BLOS1也参与了BLOC-1相关复合体(BORC)。由于BLOS1基因敲除小鼠胚胎早期的致死性，BLOS1在上述两个复合体中的功能以及是否具有新的功能尚不清楚。在这里，我们产生了三个斑马鱼突变系，由于BLOCK-1，BLOCK 1s2和dtnbp1a的突变，黑色素和银色素的形成减弱，这表明它们在同一个复合体中起作用。此外，BLOC1s1和BLOC1s2的突变导致顶盖后部聚集了成簇的溶酶体小泡，这代表了斑马鱼中BORC特有的功能。此外，BLOCK 1s1在胚胎后阶段的游泳组织中高度表达，是正向调节基因表达所必需的，该基因调控哺乳动物肺表面活性物质的产生和肺发育。我们的研究确定BLOS1是表面活性物质系统的重要调节因子。因此，斑马鱼的泳囊可能是一个容易的系统来筛选和研究控制表面活性物质产生和动态平衡的遗传修饰物。
Hermansky-Pudlak syndrome (HPS) is a human autosomal recessive disorder that is characterized by oculocutaneous albinism and a deficiency of the platelet storage pool resulting from defective biogenesis of lysosome-related organelles (LROs). To date, 10 HPS genes have been identified, three of which belong to the octamer complex BLOC-1 (biogenesis of lysosome-related organelles complex 1). One subunit of the BLOC-1 complex, BLOS1, also participates in the BLOC-1-related complex (BORC). Due to lethality at the early embryo stage in BLOS1 knockout mice, the function of BLOS1 in the above two complexes and whether it has a novel function are unclear. Here, we generated three zebrafish mutant lines with a BLOC-1 deficiency, in which melanin and silver pigment formation was attenuated as a result of mutation of bloc1s1, bloc1s2, and dtnbp1a, suggesting that they function in the same complex. In addition, mutations of bloc1s1 and bloc1s2 caused an accumulation of clusters of lysosomal vesicles at the posterior part of the tectum, representing a BORC-specific function in zebrafish. Moreover, bloc1s1 is highly expressed in the swimbladder during postembryonic stages and is required for positively regulating the expression of the genes, which is known to govern surfactant production and lung development in mammals. Our study identified BLOS1 as a crucial regulator of the surfactant system. Thus, the zebrafish swimbladder might be an easy system to screen and study genetic modifiers that control surfactant production and homeostasis.