title: Apolipoprotein A-I increases association of cytosolic cholesterol and caveolin-1 with microtubule cytoskeletons in rat astrocytes.
abstract: Apolipoprotein (apo) A-I induces rapid translocation of protein kinase Calpha and phospholipase Cgamma, and slow translocation of caveolin-1 and newly synthesized cholesterol to the cytosolic lipid-protein particle (CLPP) fraction in rat astrocytes. In order to understand the function of CLPP, we investigated the interaction with cytoskeletons of CLPP-related proteins such as caveolin-1 and protein kinase Calpha and of CLPP-related lipids in rat astrocytes. Under the conditions that microtubules were depolymerized, association of cytosolic caveolin-1 with protein kinase Calpha and alpha-tubulin was enhanced when the cells were treated with apoA-I for 5 min. This association was suppressed by a scaffolding domain-peptide of caveolin-1. Association with the microtubule-like filaments of cytosolic lipids, caveolin-1 and protein kinase Calpha was also increased by the apoA-I treatment and inhibited by the scaffolding domain peptide. Paclitaxel (taxol), a compound to stabilize microtubules, suppressed the apoA-I-mediated intracellular translocation and release from the cells of the de novo synthesized cholesterol and phospholipid. The findings suggested that the association of CLPP with microtubules is mediated by a scaffolding domain of caveolin-1, induced by apoA-I and involved in regulation of intracellular cholesterol trafficking for assembly of cellular lipids to apoA-I-high-density lipoprotein (HDL).
authors.affiliation: Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Jin-ichi
authors.initials: J
authors.lastname: Ito
authors.forename: Alireza
authors.initials: A
authors.lastname: Kheirollah
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nagayasu
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051242:Caveolin 1 / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008075:Lipoproteins, HDL / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D016632:Apolipoprotein A-I; D051242:Caveolin 1; D008075:Lipoproteins, HDL; D010455:Peptides; D014404:Tubulin; D002784:Cholesterol; D051571:Protein Kinase C-alpha; D017239:Paclitaxel