The role of the Lowe syndrome protein OCRL in the endocytic pathway.
Mutations of the inositol-5-phosphatase OCRL cause Lowe syndrome and Dent-II disease. Both are rare genetic disorders characterized by renal defects. Lowe syndrome is furthermore characterized by defects of the eye (congenital cataracts) and nervous system (mental disabilities, hypotonia). OCRL has been localised to various endocytic compartments suggesting impairments in the endocytic pathway as possible disease mechanism. Recent evidence strongly supports this view and shows essential roles of OCRL at clathrin coated pits, transport of cargo from endosomes to the trans-Golgi network as well as recycling of receptors from endosomes to the plasma membrane. In particular in vitro and in vivo evidence demonstrates an important role of OCRL in recycling of megalin, a multi-ligand receptor crucial for reabsorption of nutrients in the proximal tubulus, a process severely impaired in Lowe syndrome patients. Thus defects in the endocytic pathway are likely to significantly contribute to the kidney phenotype in Lowe syndrome and Dent-II disease.
Shruti
S
Sharma
Agnieszka
A
Skowronek
Kai Sven
KS
Erdmann
D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D009800:Oculocerebrorenal Syndrome / Q000503:physiopathology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human