• Login
    View Item 
    •   Home
    • Colleges & Programs
    • Medical College of Georgia (MCG)
    • Department of Neurology
    • Department of Neurology: Faculty Research and Presentations
    • View Item
    •   Home
    • Colleges & Programs
    • Medical College of Georgia (MCG)
    • Department of Neurology
    • Department of Neurology: Faculty Research and Presentations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Scholarly CommonsCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    About

    AboutCreative CommonsAugusta University LibrariesUSG Copyright Policy

    Statistics

    Display statistics

    Lowe Syndrome Protein OCRL1 Supports Maturation of Polarized Epithelial Cells

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    pone.0024044.pdf
    Size:
    1.100Mb
    Format:
    PDF
    Download
    Authors
    Grieve, Adam G.
    Daniels, Rachel D.
    Sanchez-Heras, Elena
    Hayes, Matthew J.
    Moss, Stephen E.
    Matter, Karl
    Lowe, Martin
    Levine, Timothy P.
    Issue Date
    2011-08-25
    URI
    http://hdl.handle.net/10675.2/755
    
    Metadata
    Show full item record
    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 a-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.
    Citation
    PLoS One. 2011 Aug 25; 6(8):e24044
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0024044
    Scopus Count
    Collections
    Department of Neurology: Faculty Research and Presentations

    entitlement

    Related articles

    • Structure and function of the Lowe syndrome protein OCRL1.
    • Authors: Lowe M
    • Issue date: 2005 Sep
    • OCRL1 modulates cilia length in renal epithelial cells.
    • Authors: Rbaibi Y, Cui S, Mo D, Carattino M, Rohatgi R, Satlin LM, Szalinski CM, Swanhart LM, Fölsch H, Hukriede NA, Weisz OA
    • Issue date: 2012 Sep
    • Crystal structure of the Rab binding domain of OCRL1 in complex with Rab8 and functional implications of the OCRL1/Rab8 module for Lowe syndrome.
    • Authors: Hagemann N, Hou X, Goody RS, Itzen A, Erdmann KS
    • Issue date: 2012 Apr-Jun
    • Zonula occludens-1 and -2 regulate apical cell structure and the zonula adherens cytoskeleton in polarized epithelia.
    • Authors: Fanning AS, Van Itallie CM, Anderson JM
    • Issue date: 2012 Feb
    • Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.
    • Authors: Jänne PA, Suchy SF, Bernard D, MacDonald M, Crawley J, Grinberg A, Wynshaw-Boris A, Westphal H, Nussbaum RL
    • Issue date: 1998 May 15
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.