1. Figure 5 Cellular alterations that result from dysfunctional OCRL
Figure 5 | Cellular alterations that result from dysfunctional OCRL. a | The endolysosomal pathway in healthy proximal tubule cells. b |Loss of functional OCRL induces defects in the endolysosomal system and at the primary cilium. In particular, proximal tubular cells from patients with Lowe syndrome are characterized by an increase in clathrin-coated vesicles that fail to lose their coat, the presence of actin comets at the clathrin-coated vesicles and an increase in PI(4,5)P2 levels at the early endosome with the concomitant polymerization of actin on these intracellular membranes. This actin polymerization leads to impaired trafficking of receptors through the early endosomes, resulting in reduced recycling back to the plasma membrane, reduced activity of the retrograde pathway to the Golgi complex and reduced sorting of cargo to lysosomes. Furthermore, in the absence of OCRL, PI(4,5)P2 accumulates on autolysosomal membranes causing defective autophagic flux and an accumulation of autophagosomes. The primary cilium is also affected by the absence of OCRL: fibroblasts from patients with Lowe syndrome show evidence of defective ciliogenesis.
De Matteis, M. A. et al. (2017) The 5‑phosphatase OCRL in Lowe syndrome and Dent disease 2
Nat. Rev. Nephrol. doi: /nrneph