ApoA-IHDL Generation and Intracellular Cholesterol Transport through Cytosolic Lipid-Protein Particles in Astrocytes

الملخص EN

Exogenous apolipoprotein A-I (apoA-I) associates with ATP-binding cassette transporter A1 (ABCA1) on the cell surface of astrocytes like various peripheral cells and enhances the translocation of newly synthesized cholesterol from the endoplasmic reticulum/Golgi apparatus (ER/Golgi) to the cytosol.

The cholesterol translocated to the cytosol is incorporated to cytosolic lipid-protein particles (CLPP) together with phospholipids and proteins such as sphingomyelin, phosphatidylcholine, caveolin-1, protein kinase Cα (PK-Cα), and cyclophilin A.

The CLPP are high density lipoproteins- (HDL-)like cytosolic lipid-protein complex with densities of 1.09–1.16 g/mL and diameters of 17-18 nm.

The association of exogenous apoA-I with cellular ABCA1 induces tyrosine phosphorylation, activation, and translocation to the CLPP of ABCA1-associated phospholipase Cγ (PL-Cγ) in rat astrocytes.

Furthermore, PK-Cα is translocated and activated to/in the CLPP through the production of diacylglyceride in the CLPP.

ApoA-I enhances both the association of CLPP with microtubules and the phosphorylation of α-tubulin as a component of microtubules.

The CLPP are dissociated from microtubules after α-tubulin in microtubules is phosphorylated by the CLPP-associated PK-Cα.

The association and dissociation between CLPP and microtubules may participate in the intracellular transport of cholesterol to the plasma membrane.