From bowel to kidneys: the role of cubilin in physiology and disease

Abstract

Cubilin is a large endocytic receptor serving such diverse functions as the intestinal absorption of the intrinsic factor-B(12) complex and the renal proximal tubule reabsorption of filtered proteins including albumin, transferrin, vitamin D-binding protein and other important plasma carriers. Cubilin is a structurally unique, peripheral membrane protein, which depends on the membrane protein amnionless (AMN) for correct apical translocation. In addition, AMN appears important for efficient internalization of intrinsic factor-B(12) in the intestine, whereas in the proximal tubule cubilin interacts with another endocytic receptor, megalin, for effective reabsorption. The importance of cubilin has been demonstrated in several animal models of cubilin deficiency as well as in a variety of human diseases. Recent demonstration of cubilin in podocytes from various species awaits further clarification with respect to the functional role as well as its role in pathology.

Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans

“…Therefore, the association with T2D-ESRD seems credible. Cubilin is a 460-kD multipurpose receptor that can bind to a range of ligands, including intrinsic factor/vitamin B12, transferrin, hemoglobin, HDL cholesterol, apolipoprotein A1, megalin, and albumin (32). As a peripheral membrane protein, cubilin contains a 110-residue N-terminal domain, an eight EGF-like repeat domain, and 27 CUB domains (33).…”

Amelioration of anti-tuberculosis drug induced oxidative stress in kidneys bySpirulina fusiformisin a rat model

“…24 It has also been shown in many previous studies that vitamin B 12 plays a major role in the metabolism of lipids through receptors such as cubilin. 25,26 The third active compound selected, phycocyanobilin, is known for its antioxidant properties and may play an important role in bringing down the oxidative stress induced by the accumulation of immune complexes and their resulting inflammatory response. 27,28 In our docking experiments, we have tried to look at the affinity of these three selected active compounds to LXR and FXR during any direct interaction.…”

Lack of megalin expression in adult human terminal ileum suggests megalin-independent cubilin/amnionless activity during vitamin B12absorption

“…); megalin can bind to cubilin, and most importantly: megalin deficiency or megalin malfunction results in loss of some cubilin ligands into the urine (Nielsen and Christensen ; Christensen et al. , ; Storm et al. ).…”

“…), and (2) patients expressing no or functionally defect megalin do not appear to suffer from B 12 ‐malabsorption (Christensen et al. ; Storm et al. ).…”