Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule

Citation
Ei. Christensen et H. Birn, Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule, AM J P-REN, 280(4), 2001, pp. F562-F573
Citations number
101
Language
INGLESE
art.tipo
Review
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN journal
0363-6127 → ACNP
Volume
280
Issue
4
Year of publication
2001
Pages
F562 - F573
Database
ISI
SICI code
0363-6127(200104)280:4<F562:MACSER>2.0.ZU;2-J
Abstract
The multiligand, endocytic receptors megalin and cubilin are colocalized in the renal proximal tubule. They are heavily expressed in the apical endocy tic apparatus. Megalin is a 600-kDa transmembrane protein belonging to the low-density lipoprotein-receptor family. The cytoplasmic tail contains thre e NPXY motifs that mediate the clustering in coated pits and are possibly i nvolved in signaling functions. Cubilin, also known as the intestinal intri nsic factor-cobalamin receptor, is a 460-kDa receptor with no transmembrane domain and no known signal for endocytosis. Because the two receptors bind each other with high affinity and colocalize in several tissues, it is hig hly conceivable that megalin mediates internalization of cubilin and its li gands. Both receptors are important for normal tubular reabsorption of prot eins, including albumin. Among the proteins normally filtered in the glomer uli, cubilin has been shown to bind albumin, immunoglobulin light chains, a nd apolipoprotein A-I. The variety of filtered ligands identified for megal in include vitamin- binding proteins, hormones, enzymes, apolipoprotein H, albumin, and beta (2)- and alpha (1)-microglobulin. Loss of these proteins and vitamins in the urine of megalin-deficient mice illustrates the physiol ogical importance of this receptor.