A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans.
A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans.
复制标题
秀丽隐杆线虫超大脂滴突变体的遗传筛查。
DOI：
10.1534/g3.116.030866
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发表时间：
2016-08-09
期刊：
影响因子：
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通讯作者：
Zhang SO
中科院分区：
文献类型：
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作者：
Li S;Xu S;Ma Y;Wu S;Feng Y;Cui Q;Chen L;Zhou S;Kong Y;Zhang X;Yu J;Wu M;Zhang SO
为了识别调节脂滴(LD)大小动态的基因，我们使用了遗传易驯化的模式生物秀丽线虫，其野生型LD种群显示出稳定的大小状态，最大直径为3μm。从6.7×10 5个突变的单倍体基因组的饱和正向遗传筛选中，我们分离到118个超大肠道LDs常达10μm的突变株，这些突变株除4个已知基因(maoc-1、dhs-28、daf-22和prx-10)外，还定义了9个新的互补组。这9组被命名为Drop(脂滴异常)，并分为四类。与Prx-10类似，I类突变体Drop-5和Drop-9在依赖ACS-22-DGAT-2的LD生长中上调，对LD水解性耐受，在过氧化物体输入方面存在缺陷。第二类突变体Drop-2、Drop-3、Drop-6和Drop-7在Ld生长中上调，对Ld水解性耐受，但在过氧化体输入方面没有缺陷。III类突变体Drop-1和Drop-8在LD生长中既不上调，也不抵抗LD水解，但在LD融合中似乎上调。第四类突变体Drop-4被克隆为SAMS-1，与其他三类不同，Drop-4不依赖于ACS-22，且耐水解。这四类超大小的LD突变体对于LD细胞过程的机制研究，包括生长、水解和融合，应该是有价值的。
To identify genes that regulate the dynamics of lipid droplet (LD) size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild-type LD population displays a steady state of size with an upper limit of 3 μm in diameter. From a saturated forward genetic screen of 6.7 × 105 mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 μm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10). The nine groups are named drop (lipid droplet abnormal) and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22-DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up-regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion.