Apolipoprotein A-II is catabolized in the kidney as a function of its plasma concentration.
We investigated in vivo catabolism of apolipoprotein A-II (apo A-II), a major determinant of plasma HDL levels. Like apoA-I, murine apoA-II (mapoA-II) and human apoA-II (hapoA-II) were reabsorbed in the first segment of kidney proximal tubules of control and hapoA-II-transgenic mice, respectively. ApoA-II colocalized in brush border membranes with cubilin and megalin (the apoA-I receptor and coreceptor, respectively), with mapoA-I in intracellular vesicles of tubular epithelial cells, and was targeted to lysosomes, suggestive of degradation. By use of three transgenic lines with plasma hapoA-II concentrations ranging from normal to three times higher, we established an association between plasma concentration and renal catabolism of hapoA-II. HapoA-II was rapidly internalized in yolk sac epithelial cells expressing high levels of cubilin and megalin, colocalized with cubilin and megalin on the cell surface, and effectively competed with apoA-I for uptake, which was inhibitable by anti-cubilin antibodies. Kidney cortical cells that only express megalin internalized LDL but not apoA-II, apoA-I, or HDL, suggesting that megalin is not an apoA-II receptor. We show that apoA-II is efficiently reabsorbed in kidney proximal tubules in relation to its plasma concentration.
Dugué-Pujol
Sonia
S
Institut National de la Santé et de la Recherche Médicale, U872, Equipe 6, Paris, France.
Rousset
Xavier
X
Château
Danielle
D
Pastier
Danièle
D
Klein
Christophe
C
Demeurie
Jeannine
J
Cywiner-Golenzer
Charlotte
C
Chabert
Michèle
M
Verroust
Pierre
P
Chambaz
Jean
J
Châtelet
François-Patrick
FP
Kalopissis
Athina-Despina
AD
D000818:Animals; D016633:Apolipoprotein A-II / Q000097:blood* / Q000378:metabolism*; D001053:Apolipoproteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D008297:Male; D008660:Metabolism; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D015017:Yolk Sac / Q000378:metabolism
D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor