Grieve, AG;
Daniels, RD;
Sanchez-Heras, E;
Hayes, MJ;
Moss, SE;
Matter, K;
Lowe, M;
(2011)
Lowe Syndrome Protein OCRL1 Supports Maturation of Polarized Epithelial Cells.
PLOS ONE
, 6
(8)
, Article e24044. 10.1371/journal.pone.0024044.
![[thumbnail of 1321730.pdf]](https://discovery-pp.ucl.ac.uk/style/images/fileicons/application_pdf.png) Preview |
PDF
1321730.pdf Available under License : See the attached licence file. Download (1MB) |
Abstract
Mutations in the inositol polyphosphate 5-phosphatase OCRL1 cause Lowe Syndrome, leading to cataracts, mental retardation and renal failure. We noted that cell types affected in Lowe Syndrome are highly polarized, and therefore we studied OCRL1 in epithelial cells as they mature from isolated individual cells into polarized sheets and cysts with extensive communication between neighbouring cells. We show that a proportion of OCRL1 targets intercellular junctions at the early stages of their formation, co-localizing both with adherens junctional components and with tight junctional components. Correlating with this distribution, OCRL1 forms complexes with junctional components alpha-catenin and zonula occludens (ZO)-1/2/3. Depletion of OCRL1 in epithelial cells growing as a sheet inhibits maturation; cells remain flat, fail to polarize apical markers and also show reduced proliferation. The effect on shape is reverted by re-expressed OCRL1 and requires the 5'-phosphatase domain, indicating that down-regulation of 5-phosphorylated inositides is necessary for epithelial development. The effect of OCRL1 in epithelial maturation is seen more strongly in 3-dimensional cultures, where epithelial cells lacking OCRL1 not only fail to form a central lumen, but also do not have the correct intracellular distribution of ZO-1, suggesting that OCRL1 functions early in the maturation of intercellular junctions when cells grow as cysts. A role of OCRL1 in junctions of polarized cells may explain the pattern of organs affected in Lowe Syndrome.
| Type: | Article |
|---|---|
| Title: | Lowe Syndrome Protein OCRL1 Supports Maturation of Polarized Epithelial Cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0024044 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0024044 |
| Language: | English |
| Additional information: | © 2011 Grieve et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | INOSITOL POLYPHOSPHATE 5-PHOSPHATASE, TRANS-GOLGI NETWORK, TRANSCRIPTION FACTOR ZONAB/DBPA, APICAL JUNCTIONAL COMPLEX, TIGHT JUNCTION, PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE, PLASMA-MEMBRANE, PARACELLULAR PERMEABILITY, MORPHOGENESIS, DOMAIN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1321730 |
Archive Staff Only
 |
View Item |
