| Phosphatidylinositol 4-kinase IIα is palmitoylated by Golgi-localized palmitoyltransferases in cholesterol-dependent manner. | |
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MedLine Citation:
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PMID: 22535966 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Dongmei Lu; Hui-qiao Sun; Hanzhi Wang; Barbara Barylko; Yuko Fukata; Masaki Fukata; Joseph P Albanesi; Helen L Yin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-04-25 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-06-25 Completed Date: 2012-09-20 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 21856-65 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 4-Kinase
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chemistry*,
metabolism Acyltransferases / metabolism* Amino Acid Motifs Animals COS Cells Cell Membrane / metabolism Cercopithecus aethiops Cholesterol / chemistry, metabolism* Detergents / pharmacology Gene Expression Regulation, Enzymologic Golgi Apparatus / metabolism* HEK293 Cells HeLa Cells Humans Immunoprecipitation Mice Models, Biological Palmitic Acids / chemistry* |
| Grant Support | |
ID/Acronym/Agency:
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GM75401/GM/NIGMS NIH HHS; P50 GM21681/GM/NIGMS NIH HHS; R01 GM66110/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Detergents; 0/Palmitic Acids; 57-88-5/Cholesterol; EC 2.3.-/Acyltransferases; EC 2.3.-/DHHC3 protein, human; EC 2.7.1.67/1-Phosphatidylinositol 4-Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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