近日,，國際著名雜志Journal of Cell Science刊登了來自中國科學(xué)院遺傳與發(fā)育生物學(xué)研究所,，德國馬普生物物理化學(xué)研究所的研究人員的最新研究成果“Opposite and redundant roles of the two Drosophila Perilipins in lipid mobilization， ”的文章,，文章中,，研究者發(fā)現(xiàn)了果蠅中僅有的兩個(gè)PAT家族蛋白Plin1和Plin2對(duì)脂解既有相同，又有相反的調(diào)控功能,，揭示了果蠅PAT家族蛋白在脂解中的復(fù)雜功能,，為后續(xù)解析PAT家族蛋白在進(jìn)化上的功能提供了有力的理論依據(jù)。
文章的通訊作者是遺傳與發(fā)育生物學(xué)研究所黃勛研究員,，黃勛實(shí)驗(yàn)室的博士生畢俊峰和項(xiàng)延會(huì)為論文的共同第一作者,。該研究與德國馬普生物物理化學(xué)研究所Ronald P. Kühnlein實(shí)驗(yàn)室合作完成，得到了中科院,、科技部和國家自然科學(xué)基金委的資助,。
脂類是生物體內(nèi)重要的能量儲(chǔ)存形式，保持人體內(nèi)的脂類代謝平衡十分重要,。脂類代謝紊亂會(huì)導(dǎo)致高血脂,、胰島素抗性、糖尿病和脂肪肝等疾病,。在細(xì)胞中,，脂類主要是以甘油三酯和膽固醇酯等中性脂的形式儲(chǔ)存在于脂滴(lipid droplet)中。
PAT家族蛋白是一類高度保守且特異性定位于脂滴表面的蛋白,。前人的工作發(fā)現(xiàn),，PAT家族蛋白參與脂解的調(diào)控。但是,，體內(nèi)PAT家族蛋白成員之間是如何分工協(xié)調(diào)脂解仍然不太清楚,。
在這篇文章中,，研究人員以果蠅為模式生物，發(fā)現(xiàn)了果蠅中僅有的兩個(gè)PAT家族蛋白Plin1和Plin2對(duì)脂解既有相同,，又有相反的調(diào)控功能,。通過對(duì)Plin1和Plin2突變體和過表達(dá)株系脂肪細(xì)胞的表型分析發(fā)現(xiàn)，Plin1促進(jìn)了脂解,，而Plin2抑制了脂解。
進(jìn)一步研究發(fā)現(xiàn),，Plin1對(duì)于脂酶HSL從細(xì)胞質(zhì)定位到脂滴表面是必須的,。在Plin1和Plin2雙突變體脂肪細(xì)胞中，脂滴大小和脂類含量要明顯低于Plin1和Plin2的單突變體,，說明Plin1還具有抑制脂解的功能,。研究同時(shí)還發(fā)現(xiàn)，Plin1特有的C端區(qū)域決定了其與Plin2之間功能的不同,。
這項(xiàng)研究揭示了果蠅PAT家族蛋白在脂解中的復(fù)雜功能,，為后續(xù)解析PAT家族蛋白在進(jìn)化上的功能提供了有力的理論依據(jù)。
黃勛研究員早年畢業(yè)于廈門大學(xué),，2006年起任中國科學(xué)院遺傳與發(fā)育生物學(xué)研究所研究員,，入選百人計(jì)劃，主要研究方向是動(dòng)物發(fā)育與疾病的遺傳調(diào)控,。
去年其實(shí)驗(yàn)室曾在PLoS Genetics雜志上發(fā)表文章,，揭示了脂類異位儲(chǔ)積的新機(jī)制。新研究發(fā)現(xiàn)為后續(xù)大規(guī)模挖掘控制脂滴異位累積的基因,，闡明其分子機(jī)理奠定了基礎(chǔ),。（生物谷Bioon.com）
doi:10.1242/jcs.101329
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Opposite and redundant roles of the two Drosophila Perilipins in lipid mobilization
Junfeng Bi*, Yanhui Xiang*, Haiyang Chen, Zhonghua Liu, Sebastian Grönke, Ronald P. Kühnlein and Xun Huang#
Lipid droplets are the main lipid storage sites in cells. Lipid droplet homeostasis is regulated by the surface accessibility of lipases. Mammalian adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are two key lipases for basal and stimulated lipolysis, respectively. Perilipins, the best known lipid droplet surface proteins, can either recruit lipases or prevent the access of lipases to lipid droplets. Mammals have five Perilipins, which often exhibit redundant functions, precluding the analysis of the exact role of individual Perilipin in vivo. Drosophila has only two Perilipins, PLIN1/LSD-1 and PLIN2/LSD-2. Previous studies revealed that PLIN2 is important for protecting lipid droplets from lipolysis mediated by Brummer (BMM), the Drosophila homolog of ATGL. In this study, we report the functional analysis of PLIN1 and Drosophila HSL (dHSL). Loss-of-function and overexpression studies reveal that as opposed to PLIN2, PLIN1 likely facilitates lipid mobilization. dHSL is recruited from the cytosol to the surface of lipid droplets under starved conditions and PLIN1 is necessary for the starved induced lipid droplet localization of dHSL. Moreover, phenotypic analysis of plin1;plin2 double mutants revealed that PLIN1 and PLIN2 may have redundant functions in protecting lipid droplets from lipolysis. Therefore, the two Drosophila Perilipins have both opposite and redundant roles. Domain swapping and deletion analyses indicate that the C-terminal region of PLIN1 confers functional specificity on PLIN1. Our study highlights the complex roles of Drosophila Perilipins proteins and the evolutionarily conserved regulation of HSL translocation by Perilipins.
