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

Adam J. Aitchison, Daniel J. Arsenault, Neale D. Ridgway

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

53 Citas (Scopus)

Resumen

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 cells. During 3T3-L1 and human preadipocyte differentiation, CCTα expression and PC synthesis was induced. In 3T3-L1 cells, CCTα 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 CCTα regulated LD size but did not affect TAG storage or adipogenesis. LD biogenesis in nonadipocyte cell lines treated with oleate also promoted CCTα translocation to the nuclear envelope and/or cytoplasm but not LDs. In rat intestinal epithelial cells, CCTα silencing increased LD size, but LD number and TAG deposition were decreased due to oleate-induced cytotoxicity. We conclude that CCTα increases PC synthesis for LD biogenesis by translocation to the nuclear envelope and not cytoplasmic LDs.

Idioma originalEnglish
Páginas (desde-hasta)2927-2938
Número de páginas12
PublicaciónMolecular Biology of the Cell
Volumen26
N.º16
DOI
EstadoPublished - ago. 15 2015

Nota bibliográfica

Publisher Copyright:
© 2015 Barbosa, Carreira, et al.

ASJC Scopus Subject Areas

  • Molecular Biology
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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