Caveolin-1--a novel interacting partner of organic cation/carnitine transporter (Octn2): effect of protein kinase C on this interaction in rat astrocytes.

OCTN2--the Organic Cation Transporter Novel family member 2 (SLC22A5) is known to be a xenobiotic/drug transporter. It transports as well carnitine--a compound necessary for oxidation of fatty acids and mutations of its gene cause primary carnitine deficiency. Octn2 regulation by protein kinase C was studied in rat astrocytes--cells in which β-oxidation takes place in the brain. Activation of with phorbol ester stimulated L-carnitine transport and increased cell surface presence of the transporter, although no phosphorylation of Octn2 could be detected. duanyu1531 activation resulted in an augmented Octn2 presence in cholesterol/sphingolipid-rich microdomains of plasma membrane (rafts) and increased co-precipitation of Octn2 with raft-proteins, caveolin-1 and flotillin-1. Deletion of potential caveolin-1 binding motifs pointed to amino acids 14-22 and 447-454 as the caveolin-1 binding sites within Octn2 sequence. A direct interaction of Octn2 with caveolin-1 in astrocytes upon duanyu1531 activation was detected by proximity ligation assay, while such an interaction was excluded in case of flotillin-1. Functioning of a multi-protein complex regulated by duanyu1531 has been postulated in rOctn2 trafficking to the cell surface, a process which could be important both under physiological conditions, when carnitine facilitates fatty acids catabolism and controls free pool as well as in pathology, when transport of several drugs can induce secondary carnitine deficiency.

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