1. Figure 1 The endolysosomal pathway in proximal
tubular cells and the disease genes that cause renal Fanconi syndrome
Figure 1 | The endolysosomal pathway in proximal tubular cells and the disease genes that cause renal Fanconi syndrome. Tubular epithelial cells use clathrin-mediated endocytosis (1), trafficking to the lysosomes (2) and transcytosis (3) to internalize and process cargo, such as albumin, immunoglobulins and vitamins. Recycling of cargo from the early endosomes back to the apical plasma membrane (4) is required for a new cycle of cargo binding and internalization to occur. The inability to internalize or process cargo (such as proteins) is a feature of renal Fanconi syndrome and can be genetic or acquired. The genes of the endolysosomal pathway, which when mutated cause renal Fanconi syndrome are shown in boxes, along with the associated genetic diseases. These genes include those that encode endocytic receptors and their accessory proteins (for example, LRP2, whichencodes the multiligand receptor megalin; CUBN, whichencodes cubilin; and AMN, whichencodes the cubilin-associated protein amnionless). Renal Fanconi syndrome can also be caused by mutations in genes that encode components of the endolysosomal pathway (for example OCRL, which encodes the inositol polyphosphate 5-phosphatase OCRL-1; CLCN5, which encodes the endosomal chloride channel ClC-5; CTNS, which encodes the cystine transporter cystinosin; GLA, whichencodes α-galactosidase A; VPS33B, which encodes the vacuolar protein sorting-associated protein 33B that is involved in sorting cargo to the late endosome and lysosomes; and VIPAS39 (the gene product of which interacts with VPS33B to regulate apical–basolateral polarity).
De Matteis, M. A. et al. (2017) The 5‑phosphatase OCRL in Lowe syndrome and Dent disease 2
Nat. Rev. Nephrol. doi: /nrneph