Characterization of the Interaction of Neuropathy Target Esterase with the Endoplasmic Reticulum and Lipid Droplets

被引:13
作者
Chang, Pingan [1 ]
He, Lin [1 ]
Wang, Yu [1 ]
Heier, Christoph [2 ]
Wu, Yijun [3 ]
Huang, Feifei [1 ]
机构
[1] Chongqing Univ Posts & Telecommun, Sch Bioinformat, Chongqing Key Lab Big Data Biointelligence, Chongqing 400065, Peoples R China
[2] Karl Franzens Univ Graz, Inst Mol Biosci, A-8010 Graz, Austria
[3] Chinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects, Beijing 100101, Peoples R China
关键词
neuropathy target esterase; PNPLA6; lipid droplet; endoplasmic reticulum; triacylglycerol; lysophospholipase; PHOSPHATIDYLCHOLINE SYNTHESIS; CATALYTIC DOMAIN; MUTATIONS; FAILURE; LINKS;
D O I
10.3390/biom9120848
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neuropathy target esterase (NTE) is an endoplasmic reticulum (ER)-localized phospholipase that deacylates phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Loss-of-function mutations in the human NTE gene have been associated with a spectrum of neurodegenerative disorders such as hereditary spastic paraplegia, ataxia and chorioretinal dystrophy. Despite this, little is known about structure-function relationships between NTE protein domains, enzymatic activity and the interaction with cellular organelles. In the current study we show that the C-terminal region of NTE forms a catalytically active domain that exhibits high affinity for lipid droplets (LDs), cellular storage organelles for triacylglycerol (TAG), which have been recently implicated in the progression of neurodegenerative diseases. Ectopic expression of the C domain in cultured cells decreases cellular PC, elevates TAG and induces LD clustering. LD interactions of NTE are inhibited by default by a non-enzymatic regulatory (R) region with three putative nucleotide monophosphate binding sites. Together with a N-terminal TMD the R region promotes proper distribution of the catalytic C-terminal region to the ER network. Taken together, our data indicate that NTE may exhibit dynamic interactions with the ER and LDs depending on the interplay of its functional regions. Mutations that disrupt this interplay may contribute to NTE-associated disorders by affecting NTE positioning.
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页数:16
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