ArticleThe Journal of biological chemistry2018
Phosphoinositide binding by the PH domain in ceramide transfer protein (CERT) is inhibited by hyperphosphorylation of an adjacent serine-repeat motif.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Phenotypic and Genotypic Associations Between Migraine and Lipoprotein Subfractions.Neurology · 2021Pooled it
- Decoding the Sphingolipid Landscape of Clear Cell Renal Cell Carcinoma: A Single-Cell-Guided Prognostic Model Built With 101 Machine Learning.Human mutation · 2026Article
- Emerging roles of lipid transfer protein dimerization.Journal of cell science · 2025Review
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Targeting membrane contact sites to mediate lipid dynamics: innovative cancer therapies.Cell communication and signaling : CCS · 2025Review
- The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi.The Journal of cell biology · 2023Article
- CERT1 mutations perturb human development by disrupting sphingolipid homeostasis.The Journal of clinical investigation · 2023Article
- Creating and sensing asymmetric lipid distributions throughout the cell.Emerging topics in life sciences · 2023Article
- 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
- Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer.International journal of molecular sciences · 2021Review
- FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts.The EMBO journal · 2020Article
- Lipid Exchangers: Cellular Functions and Mechanistic Links With Phosphoinositide Metabolism.Frontiers in cell and developmental biology · 2020Review
- Unicellular ancestry and mechanisms of diversification of Goodpasture antigen-binding protein.The Journal of biological chemistry · 2019 · on this mapArticle
- Both the N- and C- terminal regions of the Chlamydial inclusion protein D (IncD) are required for interaction with the pleckstrin homology domain of the ceramide transport protein CERT.Biochemical and biophysical research communications · 2018Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingolipids such as ceramide are important constituents of cell membranes. The ceramide transfer protein (CERT) moves ceramide from the endoplasmic reticulum to the Golgi apparatus in a nonvesicular manner. Hyperphosphorylation of the serine-repeat motif (SRM) adjacent to the pleckstrin homology (PH) domain of CERT down-regulates the inter-organelle ceramide transport function of CERT. However, the mechanistic details of this down-regulation remain elusive. Using solution NMR and binding assays, we herein show that a hyperphosphorylation-mimetic CERT variant in which 10 serine/threonine residues of SRM had been replaced with glutamate residues (the 10E variant) displays an intramolecular interaction between SRM and positively charged regions of the PH domain, which are involved in the binding of this domain to phosphatidylinositol 4-monophosphate (PI4P). Of note, the binding of the PH domain to PI4P-embedded membranes was attenuated by the SRM 10E substitutions in cell-free assays. Moreover, the 10E substitutions reduced the Golgi-targeting activity of the PH-SRM construct in living cells. These results indicate that hyperphosphorylated SRM directly interacts with the surface of the PH domain in an intramolecular manner, thereby decreasing the PI4P-binding activity of the PH domain. In light of these findings, we propose that the hyperphosphorylation of SRM may trigger the dissociation of CERT from the Golgi apparatus, resulting in a functionally less active conformation of CERT.
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