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Nuclear-localized CTP:phosphocholine cytidylyltransferase ? regulates phosphatidylcholine synthesis required for lipid droplet biogenesis.


ABSTRACT: The reversible association of CTP:phosphocholine cytidylyltransferase ? (CCT?) with membranes regulates the synthesis of phosphatidylcholine (PC) by the CDP-choline (Kennedy) pathway. Based on results with insect CCT homologues, translocation of nuclear CCT? onto cytoplasmic lipid droplets (LDs) is proposed to stimulate the synthesis of PC that is required for LD biogenesis and triacylglycerol (TAG) storage. We examined whether this regulatory mechanism applied to LD biogenesis in mammalian cells. During 3T3-L1 and human preadipocyte differentiation, CCT? expression and PC synthesis was induced. In 3T3-L1 cells, CCT? translocated from the nucleoplasm to the nuclear envelope and cytosol but did not associate with LDs. The enzyme also remained in the nucleus during human adipocyte differentiation. RNAi silencing in 3T3-L1 cells showed that CCT? regulated LD size but did not affect TAG storage or adipogenesis. LD biogenesis in nonadipocyte cell lines treated with oleate also promoted CCT? translocation to the nuclear envelope and/or cytoplasm but not LDs. In rat intestinal epithelial cells, CCT? silencing increased LD size, but LD number and TAG deposition were decreased due to oleate-induced cytotoxicity. We conclude that CCT? increases PC synthesis for LD biogenesis by translocation to the nuclear envelope and not cytoplasmic LDs.

SUBMITTER: Aitchison AJ 

PROVIDER: S-EPMC4571330 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Nuclear-localized CTP:phosphocholine cytidylyltransferase α regulates phosphatidylcholine synthesis required for lipid droplet biogenesis.

Aitchison Adam J AJ   Arsenault Daniel J DJ   Ridgway Neale D ND  

Molecular biology of the cell 20150624 16


The reversible association of CTP:phosphocholine cytidylyltransferase α (CCTα) with membranes regulates the synthesis of phosphatidylcholine (PC) by the CDP-choline (Kennedy) pathway. Based on results with insect CCT homologues, translocation of nuclear CCTα onto cytoplasmic lipid droplets (LDs) is proposed to stimulate the synthesis of PC that is required for LD biogenesis and triacylglycerol (TAG) storage. We examined whether this regulatory mechanism applied to LD biogenesis in mammalian cell  ...[more]

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