Apolipoprotein D Internalization Is a Basigin-dependent Mechanism.
Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have 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. Down-regulation 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, competitively reduced 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.
From the Laboratoire de Biologie Moléculaire and.
Ouafa
O
Najyb
Laboratoire du Métabolisme des Lipoprotéines, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal, Succursale Centre-ville, Montréal, Quebec H3C 3P8, Canada.
Louise
L
Brissette
From the Laboratoire de Biologie Moléculaire and rassart.eric@uqam.ca.
Eric
E
Rassart
D053399:Apolipoproteins D / Q000235:genetics / Q000378:metabolism*; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D006801:Humans; D021381:Protein Transport
D053399:Apolipoproteins D; C497886:BSG protein, human; D051926:Basigin
apolipoprotein D (apoD), basigin, internalization, cyclophilin A, human neuroblastoma