ArticleThe Journal of biological chemistry2014
Phosphoregulation of the ceramide transport protein CERT at serine 315 in the interaction with VAMP-associated protein (VAP) for inter-organelle trafficking of ceramide in mammalian cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 90 citations in OpenAlex.
- STARD3 regulates lysosome positioning and contacts via a GSK3-controlled phosphorylation switch.The EMBO journal · 2026Article
- Cvm1 and its paralogue Cvm2 function as a complex at vacuolar membrane contact sites.Molecular biology of the cell · 2025Article
- Targeting membrane contact sites to mediate lipid dynamics: innovative cancer therapies.Cell communication and signaling : CCS · 2025Review
- Live-Cell Identification of Inhibitors of the Lipid Transfer Protein CERT Using Nanoluciferase Bioluminescence Resonance Energy Transfer (NanoBRET).Angewandte Chemie (International ed. in English) · 2024Article
- Phosphorylation of ELYS promotes its interaction with VAPB at decondensing chromosomes during mitosis.EMBO reports · 2024Article
- Emerging roles of the Protein Phosphatase 1 (PP1) in the context of viral infections.Cell communication and signaling : CCS · 2024Review
- The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi.The Journal of cell biology · 2023Article
- Non-Vesicular Lipid Transport Machinery inInternational journal of molecular sciences · 2023Review
- CaAdvances in experimental medicine and biology · 2023Article
- Review
- Systematic analysis of membrane contact sites ineLife · 2022Article
- ER as master regulator of membrane trafficking and organelle function.The Journal of cell biology · 2022Review
- Involvement of a Cluster of Basic Amino Acids in Phosphorylation-Dependent Functional Repression of the Ceramide Transport Protein CERT.International journal of molecular sciences · 2022Article
- Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide.iScience · 2022Article
- Article
- Hyperosmotic Stress Induces Phosphorylation of CERT and Enhances Its Tethering throughout the Endoplasmic Reticulum.International journal of molecular sciences · 2022Article
- Regulating peroxisome-ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β.The Journal of cell biology · 2022Article
- Multiple Ways to Keep FFAT Under Control!Contact (Thousand Oaks (Ventura County, Calif.)) · 2022Article
- VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.Frontiers in cell and developmental biology · 2022Review
- Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer.International journal of molecular sciences · 2021Review
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ceramide transport protein CERT mediates the inter-organelle transport of ceramide for the synthesis of sphingomyelin, presumably through endoplasmic reticulum (ER)-Golgi membrane contact sites. CERT has a short peptide motif named FFAT, which associates with the ER-resident membrane protein VAP. We show that the phosphorylation of CERT at serine 315, which is adjacent to the FFAT motif, markedly enhanced the interaction of CERT with VAP. The phosphomimetic CERT S315E mutant exhibited higher activity to support the ER-to-Golgi transport of ceramide than the wild-type control in a semi-intact cell system, and this enhanced activity was abrogated when its FFAT motif was deleted. The level of phosphorylation of CERT at Ser-315 increased in HeLa cells treated with a sphingolipid biosynthesis inhibitor or exogenous sphingomyelinase. Expression of CERT S315E induced intracellular punctate structures, to which CERT and VAP were co-localized, and the occurrence of the structure was dependent on both phosphatidylinositol 4-monophosphate binding and VAP binding activities of CERT. Phosphorylation of another region (named a serine-rich motif) in CERT is known to down-regulate the activity of CERT. Analysis of various CERT mutant constructs showed that the de-phosphorylation of the serine-rich motif and the phosphorylation of Ser-315 likely have the additive contribution to enhance the activity of CERT. These results demonstrate that the phosphorylation of CERT at the FFAT motif-adjacent serine affected its affinity for VAP, which may regulate the inter-organelle trafficking of ceramide in response to the perturbation of cellular sphingomyelin and/or other sphingolipids.
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