Cross-talk between Remodeling and de Novo Pathways Maintains Phospholipid Balance through Ubiquitination*
| Autor: | Phillip L. Butler, Rama K. Mallampalli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Arginine
Mutant Phospholipid Protein degradation Biochemistry chemistry.chemical_compound symbols.namesake Mice Ubiquitin Animals Homeostasis Molecular Biology Lung Cells Cultured Phospholipids chemistry.chemical_classification biology Ubiquitination 1-Acylglycerophosphocholine O-Acyltransferase Epithelial Cells Cell Biology Receptor Cross-Talk Golgi apparatus Lipids Cell biology De novo synthesis Enzyme chemistry Diacylglycerol Cholinephosphotransferase symbols biology.protein Phosphatidylcholines lipids (amino acids peptides and proteins) Lysosomes Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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