A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells
- Yale University School of Medicine, United States
- Max Planck Institute of Biochemistry, Germany
Abstract
Mutations in the inositol 5-phosphatase OCRL cause Lowe syndrome and Dent's disease. Although OCRL, a direct clathrin interactor, is recruited to late-stage clathrin-coated pits, clinical manifestations have been primarily attributed to intracellular sorting defects. Here we show that OCRL loss in Lowe syndrome patient fibroblasts impacts clathrin-mediated endocytosis and results in an endocytic defect. These cells exhibit an accumulation of clathrin-coated vesicles and an increase in U-shaped clathrin-coated pits, which may result from sequestration of coat components on uncoated vesicles. Endocytic vesicles that fail to lose their coat nucleate the majority of the numerous actin comets present in patient cells. SNX9, an adaptor that couples late-stage endocytic coated pits to actin polymerization and which we found to bind OCRL directly, remains associated with such vesicles. These results indicate that OCRL acts as an uncoating factor and that defects in clathrin-mediated endocytosis likely contribute to pathology in patients with OCRL mutations.
Article and author information
Author details
Reviewing Editor
- Suzanne R Pfeffer, Stanford University, United States
Version history
- Received: April 1, 2014
- Accepted: August 7, 2014
- Accepted Manuscript published: August 8, 2014 (version 1)
- Version of Record published: September 18, 2014 (version 2)
Copyright
© 2014, Nández et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells
eLife 3:e02975.
https://doi.org/10.7554/eLife.02975
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