Apolipoprotein D internalization is a basigin dependent mechanism [Membrane Biology]

April 27th, 2015 by Najyb, O., Brissette, L., Rassart, E.

Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein, which binds and transports small lipophilic molecules. Expressed in several tissues, apoD is upregulated under different stress stimuli and in a variety of pathologies. Numerous studies revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration. This multifunctional protein is internalized in several cells types but the specific internalization mechanism remains unknown. In this study, we demonstrate that the internalization of apoD involves a specific cell surface receptor in 293T cells identified as the transmembrane glycoprotein basigin (BSG; CD147), more particularly its low glycosylated form. Our results show that internalized apoD colocalizes with BSG into vesicular compartments. Downregulation of BSG disrupted the internalization of apoD in cells. In contrast, overexpression of basigin in SH-5YSY cells which poorly express BSG restored the uptake of apoD. Cyclophilin A, a known ligand of BSG, reduced competitively apoD internalization confirming that BSG is a key player in the apoD internalization process. In summary, our results demonstrate that basigin is very likely the apoD receptor and provide additional clues on the mechanisms involved in apoD-mediated functions, including neuroprotection.