MLDP, a novel PAT family protein localized to lipid droplets and enriched in the heart, is regulated by peroxisome proliferator-activated receptor α
MLDP, a novel PAT family protein localized to lipid droplets and enriched in the heart, is regulated by peroxisome proliferator-activated receptor α
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DOI：
10.1074/jbc.m601682200
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发表时间：
2006-05-19
影响因子：
4.8
通讯作者：
Osumi, Takashi
中科院分区：
文献类型：
--
作者：
Yamaguchi, Tomohiro;Matsushita, Shuhei;Osumi, Takashi
胞液脂滴是一种多功能细胞器，存在于所有类型的真核细胞中，控制着脂质的稳态。在哺乳动物细胞中，LDs在其表层含有一类蛋白质，它们共享一个称为PAT结构域的同源序列，包括Perilipin、脂肪分化相关蛋白(AdRP)、一个47 kDa的尾巴相互作用蛋白(TIP47)和S3-12，它们选择性地分布在组织或细胞类型中。在某些情况下，表达受过氧化物酶体增殖物激活受体(PPAR)的调节。在这项研究中，我们在小鼠的cDNA库中发现了一个新的PAT家族成员，命名为MLDP(心肌LD蛋白)，结果表明该蛋白在心脏中高度丰富，在肝脏和肾上腺中也有较低水平的表达。亚细胞分级后，在富含LDS的顶馏分中检测到大量的MLDP。此外，过表达的绿色荧光蛋白标记的MLDP聚集在LDS表面，并与Perilipin和adrp共定位。缺失分析表明，将MLDP靶向LDS所需的N-末端区域包含PAT-1结构域和以下33-聚体结构域。PPARα的选择性配体Wy14,643在心脏和肝脏的mRNA和蛋白质水平上调MLDP，但在PPARα基因敲除的小鼠中不表达。禁食后与ADRP平行时，MLDP的表达也增加。这些结果表明MLDP是一个真正定位于LDS的新的PAT家族成员。它的表达取决于生理条件和PPARα的作用。
Cytosolic lipid droplets (LDs) are multifunctional organelles that exist in all types of eukaryotic cells and control lipid homeostasis. In mammalian cells LDs contain a class of proteins in their surface layers that share a homologous sequence called the PAT domain, including perilipin, adipose differentiation-related protein ( ADRP), a tail-interacting protein of 47 kDa (TIP47), and S3-12, which are distributed tissue- or cell type-selectively. Expression in some cases is regulated by peroxisome proliferator-activated receptors (PPARs). In this study we identified a new PAT family member named MLDP (myocardial LD protein) in a murine cDNA data base and showed the mRNA and protein to be highly enriched in the heart and also expressed at lower levels in the liver and adrenals. Upon subcellular fractionation, a substantial amount of MLDP was detected in the top fraction enriched with LDs. Furthermore, over-expressed MLDP tagged with green fluorescent protein accumulated at the surfaces of LDs and co-localized with perilipin and ADRP. Deletion analysis demonstrated the N-terminal region containing a PAT-1 domain and the following 33-mer domain to be required for targeting of MLDP to LDs. MLDP was found to be up-regulated at both mRNA and protein levels in the heart and liver by a selective ligand for PPAR alpha, Wy14,643, but not in PPAR alpha knock-out mice. MLDP expression was also increased upon fasting in parallel with ADRP. These results indicate that MLDP is a bona fide new PAT family member localized in LDs. Its expression depends on the physiological conditions and the action of PPAR alpha.