Exome sequencing reveals
cubilin mutation as a single-gene cause of proteinuria.
Accumulation of gentamicin in proximal tubule cells is due to the existence of an apical membrane endocytic complex involving the proteins megalin and
cubilin (6).
Given known interspecies differences in the functionality of megalin-associated proteins, such as
cubilin, that support megalin-mediated uptake of DBP (Amsellem et al., 2010; Nielsen et al., 2016; Nykjaer et al., 2001), a move away from animal models to experimental human studies is critical.
Birn, "Megalin and
cubilin: Multifunctional endocytic receptors," Nature Reviews Molecular Cell Biology, vol.
Birn, "Megalin and
cubilin in proximal tubule protein reabsorption: from experimental models to human disease," Kidney International, vol.
Bunn et al., "Microalbuminuria in type 1 diabetes is associated with enhanced excretion of the endocytic multiligand receptors Megalin and
Cubilin," Diabetes Care, vol.
In the proximal tubule of the glomerulus, apoA-I binds the receptors
cubilin and megalin [28], which mediate endocytosis and delivery of the protein to the lysosomes [29, 30], resulting in complete degradation of the apoA-I protein.
Human renal proximal tubular cells in suspension culture express the endocytic scavenger proteins
cubilin and megalin and the associated highly differentiated vesicular transport system not seen in 2D cultures.
[d] Excess free light chains (FLCs), readily measurable by the serum FLC assay, could disrupt the renal proximal tubule receptors megalin and
cubilin where B12 is reabsorbed [5].
Steegers-Theunissen et al., "An association study of 45 folate-related genes in spina bifida: involvement of
Cubilin (CUBN) and tRNA Aspartic Acid Methyltransferase 1 (TRDMT1)," Birth Defects Research A--Clinical and Molecular Teratology,vol.
Hojrup et al., "The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of
cubilin and amnionless," Blood, vol.