Cross-talk between Remodeling and de Novo Pathways Maintains Phospholipid Balance through Ubiquitination

Phosphatidylcholine (PtdCho), the major phospholipid of animal membranes, is generated by its remodeling and de novo synthesis. Overexpression of the remodeling enzyme, LPCAT1 (acyl-CoA:lysophosphatidylcholine acyltransferase) in epithelia decreased de novo PtdCho synthesis without significantly alt...

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Published inThe Journal of biological chemistry Vol. 285; no. 9; pp. 6246 - 6258
Main Authors Butler, Phillip L., Mallampalli, Rama K.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 26.02.2010
American Society for Biochemistry and Molecular Biology
Subjects
1-Acylglycerophosphocholine O-Acyltransferase
Animals
CELL/Epithelial
Cells, Cultured
Development Differentiation
Diacylglycerol Cholinephosphotransferase
Epithelial Cells - chemistry
Epithelial Cells - metabolism
Homeostasis
Lipids
Lung - cytology
Lysosomes - metabolism
Mice
Phosphatidylcholines - metabolism
Phospholipids - metabolism
Proteases/Ubiquitination
Protein/Degradation
Protein/Stability
Pulmonary Surfactant Apoproteins
Receptor Cross-Talk - physiology
Signal Transduction
Tissue/Organ Systems/Lung
Ubiquitin - metabolism
Ubiquitination - physiology
CELL/Epithelial
Tissue/Organ Systems/Lung
Protein/Degradation
Development Differentiation
Protein/Stability
Proteases/Ubiquitination
Pulmonary Surfactant Apoproteins
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Summary:Phosphatidylcholine (PtdCho), the major phospholipid of animal membranes, is generated by its remodeling and de novo synthesis. Overexpression of the remodeling enzyme, LPCAT1 (acyl-CoA:lysophosphatidylcholine acyltransferase) in epithelia decreased de novo PtdCho synthesis without significantly altering cellular PtdCho mass. Overexpression of LPCAT1 increased degradation of CPT1 (cholinephosphotransferase), a resident Golgi enzyme that catalyzes the terminal step for de novo PtdCho synthesis. CPT1 degradation involved its multiubiquitination and processing via the lysosomal pathway. CPT1 mutants harboring arginine substitutions at multiple carboxyl-terminal lysines exhibited proteolytic resistance to effects of LPCAT1 overexpression in cells and restored de novo PtdCho synthesis. Thus, cross-talk between phospholipid remodeling and de novo pathways involves ubiquitin-lysosomal processing of a key molecular target that mechanistically provides homeostatic control of cellular PtdCho content.
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ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.017350