ArticleThe Journal of biological chemistry2012
Phosphatidylinositol 4-kinase IIα is palmitoylated by Golgi-localized palmitoyltransferases in cholesterol-dependent manner.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 88 citations in OpenAlex.
- Article
- Cycling molecular assemblies for Golgi imaging and disruption.Nature communications · 2026Article
- Huntington's disease-associated ankyrin repeat palmitoyl transferases are rate-limiting factors in lysosome formation and fusion.PLoS genetics · 2025Article
- Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis.Nature communications · 2025Article
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- ARMH3 is an ARL5 effector that promotes PI4KB-catalyzed PI4P synthesis at the trans-Golgi network.Nature communications · 2024Article
- Identification of the GABARAP binding determinant in PI4K2A.Bioscience reports · 2024Article
- Phosphoinositide switches in cell physiology - From molecular mechanisms to disease.The Journal of biological chemistry · 2024Review
- Cyclical palmitoylation regulates TLR9 signalling and systemic autoimmunity in mice.Nature communications · 2024Article
- The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi.The Journal of cell biology · 2023Article
- Creating and sensing asymmetric lipid distributions throughout the cell.Emerging topics in life sciences · 2023Article
- High expression of PI4K2A predicted poor prognosis of colon adenocarcinoma (COAD) and correlated with immunity.Cancer medicine · 2023Article
- Phosphoinositides as membrane organizers.Nature reviews. Molecular cell biology · 2022Review
- Structural Exploration on Palmitoyltransferase DHHC3 fromPolymers · 2022Article
- Phosphoinositide transport and metabolism at membrane contact sites.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Review
- NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes.The EMBO journal · 2021Article
- Antioxidant functions of DHHC3 suppress anti-cancer drug activities.Cellular and molecular life sciences : CMLS · 2021Article
- Examining the Underappreciated Role ofFrontiers in immunology · 2021Review
- Functions of Oxysterol-Binding Proteins at Membrane Contact Sites and Their Control by Phosphoinositide Metabolism.Frontiers in cell and developmental biology · 2021Review
- Putative Role of Protein Palmitoylation in Cardiac Lipid-Induced Insulin Resistance.International journal of molecular sciences · 2020Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphatidylinositol 4-kinase IIα (PI4KIIα) is predominantly Golgi-localized, and it generates >50% of the phosphatidylinositol 4-phosphate in the Golgi. The lipid kinase activity, Golgi localization, and "integral" membrane binding of PI4KIIα and its association with low buoyant density "raft" domains are critically dependent on palmitoylation of its cysteine-rich (173)CCPCC(177) motif and are also highly cholesterol-dependent. Here, we identified the palmitoyl acyltransferases (Asp-His-His-Cys (DHHC) PATs) that palmitoylate PI4KIIα and show for the first time that palmitoylation is cholesterol-dependent. DHHC3 and DHHC7 PATs, which robustly palmitoylated PI4KIIα and were colocalized with PI4KIIα in the trans-Golgi network (TGN), were characterized in detail. Overexpression of DHHC3 or DHHC7 increased PI4KIIα palmitoylation by >3-fold, whereas overexpression of the dominant-negative PATs or PAT silencing by RNA interference decreased PI4KIIα palmitoylation, "integral" membrane association, and Golgi localization. Wild-type and dominant-negative DHHC3 and DHHC7 co-immunoprecipitated with PI4KIIα, whereas non-candidate DHHC18 and DHHC23 did not. The PI4KIIα (173)CCPCC(177) palmitoylation motif is required for interaction because the palmitoylation-defective SSPSS mutant did not co-immunoprecipitate with DHHC3. Cholesterol depletion and repletion with methyl-β-cyclodextrin reversibly altered PI4KIIα association with these DHHCs as well as PI4KIIα localization at the TGN and "integral" membrane association. Significantly, the Golgi phosphatidylinositol 4-phosphate level was altered in parallel with changes in PI4KIIα behavior. Our study uncovered a novel mechanism for the preferential recruitment and activation of PI4KIIα to the TGN by interaction with Golgi- and raft-localized DHHCs in a cholesterol-dependent manner.
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