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Apolipoprotein A‐I increases association of cytosolic cholesterol and caveolin‐1 with microtubule cytoskeletons in rat astrocytes

Apolipoprotein (apo) A‐I induces rapid translocation of protein kinase Cα and phospholipase Cγ, 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 investigat...

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Published in:Journal of neurochemistry 2006-05, Vol.97 (4), p.1034-1043
Main Authors: Ito, Jin‐ichi, Kheirollah, Alireza, Nagayasu, Yuko, Lu, Rui, Kato, Koichi, Yokoyama, Shinji
Format: Article
Language:English
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Summary:Apolipoprotein (apo) A‐I induces rapid translocation of protein kinase Cα and phospholipase Cγ, 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 Cα and of CLPP‐related lipids in rat astrocytes. Under the conditions that microtubules were depolymerized, association of cytosolic caveolin‐1 with protein kinase Cα and α‐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 Cα 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).
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2006.03805.x