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Shroom2 regulates endothelial morphogenesis and centrosome duplication through the specific sub-cellular recruitment of Rho-kinase.

Farber, Matthew J. (2012) Shroom2 regulates endothelial morphogenesis and centrosome duplication through the specific sub-cellular recruitment of Rho-kinase. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    The ability of epithelial cells to change shape is essential to the patterning of tissues and organs during development of the vertebrate embryo. Epithelial morphogenesis is mediated by the molecular regulation of cytoskeletal dynamics which underlies cellular adhesion, motility, polarity, and proliferation. The Shroom family of proteins regulates epithelial morphogenesis by promoting MyosinII-dependent changes in epithelial morphology through the ability to bind both F-actin and Rho kinase (Rock). Shroom3 is necessary to induce apical constriction of the neural epithelium and is required for proper neural tube closure during development. However, the roles of other family members are unknown. This work seeks to determine the role and mechanism of action for Shroom2 in epithelial cell biology. Through RNAi, the loss of Shroom2 reduces contractility of endothelial cells. Shroom2 physically interacts with Rock and is necessary for its cortical localization. By impeding Rock localization and reducing contractility, Shroom2 knockdown alters cytoskeletal organization, adhesion, and motility which ultimately affects in vitro angiogenesis. During these studies, it also became clear that Shroom2 localizes to the centrosome where it is required to maintain efficient centrosome duplication in a Rock-dependent manner. The results described here expand a role for the Shroom proteins in the sub-cellular localization of Rock which mediates a subset of Rock functions within epithelial cells.


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    Item Type: University of Pittsburgh ETD
    ETD Committee:
    ETD Committee TypeCommittee MemberEmail
    Committee ChairHildebrand, Jeffrey D.jeffh@pitt.edu
    Committee MemberRoman, Bethromanb@pitt.edu
    Committee MemberChapman, Deborah L.dlc7@pitt.edu
    Committee MemberDavidson, Lancelad43@pitt.edu
    Committee MemberBrodsky, Jeffreyjbrodsky@pitt.edu
    Title: Shroom2 regulates endothelial morphogenesis and centrosome duplication through the specific sub-cellular recruitment of Rho-kinase.
    Status: Published
    Abstract: The ability of epithelial cells to change shape is essential to the patterning of tissues and organs during development of the vertebrate embryo. Epithelial morphogenesis is mediated by the molecular regulation of cytoskeletal dynamics which underlies cellular adhesion, motility, polarity, and proliferation. The Shroom family of proteins regulates epithelial morphogenesis by promoting MyosinII-dependent changes in epithelial morphology through the ability to bind both F-actin and Rho kinase (Rock). Shroom3 is necessary to induce apical constriction of the neural epithelium and is required for proper neural tube closure during development. However, the roles of other family members are unknown. This work seeks to determine the role and mechanism of action for Shroom2 in epithelial cell biology. Through RNAi, the loss of Shroom2 reduces contractility of endothelial cells. Shroom2 physically interacts with Rock and is necessary for its cortical localization. By impeding Rock localization and reducing contractility, Shroom2 knockdown alters cytoskeletal organization, adhesion, and motility which ultimately affects in vitro angiogenesis. During these studies, it also became clear that Shroom2 localizes to the centrosome where it is required to maintain efficient centrosome duplication in a Rock-dependent manner. The results described here expand a role for the Shroom proteins in the sub-cellular localization of Rock which mediates a subset of Rock functions within epithelial cells.
    Date: 31 January 2012
    Date Type: Publication
    Defense Date: 15 November 2011
    Approval Date: 31 January 2012
    Submission Date: 07 December 2011
    Release Date: 31 January 2012
    Access Restriction: No restriction; The work is available for access worldwide immediately.
    Patent pending: No
    Number of Pages: 147
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    Additional Information: This updated ETD contains the proper "Kenneth P. Dietrich School of Arts and Sciences"
    Uncontrolled Keywords: Shroom, Shroom2, morphology, Rho-kinase, Rock, angiogenesis, centrosome
    Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
    Date Deposited: 31 Jan 2012 15:20
    Last Modified: 16 Jul 2014 17:04

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