Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffic at the Golgi complex

J Lipid Res. 2009 Nov;50(11):2182-92. doi: 10.1194/jlr.M800660-JLR200. Epub 2009 May 20.

Abstract

The mutant Chinese hamster ovary cell line MT58 contains a thermosensitive mutation in CTP:phosphocholine cytidylyltransferase, the regulatory enzyme in the CDP-choline pathway. As a result, MT58 cells have a 50% decrease in their phosphatidylcholine (PC) level within 24 h when cultured at the nonpermissive temperature (40 degrees C). This is due to a relative rapid breakdown of PC that is not compensated for by the inhibition of de novo PC synthesis. Despite this drastic decrease in cellular PC content, cells are viable and can proliferate by addition of lysophosphatidylcholine. By [(3)H]oleate labeling, we found that the FA moiety of the degraded PC is recovered in triacylglycerol. In accordance with this finding, an accumulation of lipid droplets is seen in MT58 cells. Analysis of PC-depleted MT58 cells by electron and fluorescence microscopy revealed a partial dilation of the rough endoplasmic reticulum, resulting in spherical structures on both sites of the nucleus, whereas the morphology of the plasma membrane, mitochondria, and Golgi complex was unaffected. In contrast to these morphological observations, protein transport from the ER remains intact. Surprisingly, protein transport at the level of the Golgi complex is impaired. Our data suggest that the transport processes at the Golgi complex are regulated by distal changes in lipid metabolism.

MeSH terms

  • Animals
  • CHO Cells
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Choline-Phosphate Cytidylyltransferase / genetics
  • Choline-Phosphate Cytidylyltransferase / metabolism
  • Cricetinae
  • Cricetulus
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Fluorescence Recovery After Photobleaching
  • Golgi Apparatus / metabolism*
  • Golgi Apparatus / ultrastructure
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lysophosphatidylcholines / pharmacology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Immunoelectron
  • Mutation
  • Oleic Acid / metabolism
  • Phosphatidylcholines / metabolism*
  • Protein Transport
  • Temperature
  • Triglycerides / metabolism
  • Tritium
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism

Substances

  • G protein, vesicular stomatitis virus
  • Lysophosphatidylcholines
  • Membrane Glycoproteins
  • Phosphatidylcholines
  • Triglycerides
  • Viral Envelope Proteins
  • Tritium
  • Green Fluorescent Proteins
  • Oleic Acid
  • Choline-Phosphate Cytidylyltransferase