Luo, N., West, C., Murga-Zamalloa, C., Sun, L., Anderson, R.M., Wells, C., Weinreb, R.N., Travers, J.B., Khanna, H., and Sun, Y. (2012) OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Human molecular genetics. 21(15):3333-3344.
Oculocerebral renal syndrome of Lowe (OCRL or Lowe syndrome), a severe X-linked congenital disorder characterized by congenital
cataracts and glaucoma, mental retardation, and kidney dysfunction, is caused by mutations in the OCRL gene. OCRL is a phosphoinositide 5-phosphatase that interacts with small GTPases and is involved in intracellular trafficking.
Despite extensive studies, it is unclear how OCRL mutations result in a myriad of phenotypes found in Lowe syndrome. Our results show that OCRL localizes to the primary cilium
of retinal pigment epithelial cells, fibroblasts, and kidney tubular cells. Lowe syndrome-associated mutations in OCRL result
in shortened cilia and this phenotype can be rescued by the introduction of wildtype OCRL; in vivo, knockdown of ocrl in zebrafish embryos results in defective cilia formation in Kupffer vesicles and cilia-dependent phenotypes. Cumulatively,
our data provide evidence for a role of OCRL in cilia maintenance and suggest the involvement of ciliary dysfunction in the
manifestation of Lowe syndrome.