Journal of Biochemistry and Biotechnology

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

Review Article - Journal of Biochemistry and Biotechnology (2018) Volume 1, Issue 1

Function of ATP-binding cassette transporter A1 (ABCA1) in apoA-Icontaining HDL generation of astroglia.

Apolipoprotein A-I (apoA-I) is one of the most abundant apolipoproteins along with apoE in the cerebrospinal fluid (CSF). It is thought that apoA-I produced by brain capillary endothelial cells in the brain, while apoE is mainly done by astrocytes. Astrocytes generate not only apoE-containing highdensity lipoprotein-like particle (apoE/HDL) using endogenous apoE but also apoA-I/HDL through the interaction with exogenous apoA-I. Astrocytes generate both apoA-I/HDL and apoE/HDL dependently on a transmembrane protein, ATP-binding cassette transporter A1 (ABCA1).ABCA1 is widely localized in both caveolin-1-rich fraction containing lipid raft domains and non-caveolin-1fraction of the plasma membrane in rat astrocytes unlike peripheral cells. Exogenous apoA-I binds to ABCA1 localized in the non-caveolin-1-fraction with slightly higher densities than the caveolin-1-rich fraction of plasma membrane but not in the complete non-caveolin-1-fraction with highest density, while the endogenous apoE is associated with ABCA1 in the caveolin-1-rich fraction of rat astrocytes. After the association with ABCA1, exogenous apoA-I stimulates the phosphorylation of ABCA1associated phospholipase C? (PL-C?) in the intracellular site and promotes the translocation of phosphorylated PL-C? to the cytosolic lipid-protein particles (CLPPs) in the cytosol fraction of rat astrocytes. The CLPPs are intracellular HDL-like lipid-protein complexes with densities of 1.09-1.16 g/ml and diameters of 17-18 nm, and composed of lipids such as cholesterol, sphingomyelin, and phosphatidylcholine with proteins such as caveolin-1, protein kinase C? (PK-C?), and cyclophilin A in astrocytes. Furthermore, the newly synthesized cholesterol is translocated along with sphingomyelin and phosphatidylcholine from the endoplasmic reticulum/Golgi apparatus (ER/Golgi) to the CLPPs in the cytosol and is transported to the plasma membrane through the interaction with microtubules. Thus, the newly synthesized cholesterol is transferred to exogenous apoA-I in the extracellular space dependently on the association of apoA-I with ABCA1 and the series of intracellular reactions in the CLPPs.

Author(s): Jin-ichi Ito

Abstract Full Text PDF