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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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Details

Item Type: University of Pittsburgh ETD
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Farber, Matthew J.mjf40@pitt.edumjf40@pitt.edu
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHildebrand, Jeffrey D.jeffh@pitt.edujeffh@pitt.edu
Committee MemberRoman, Bethromanb@pitt.eduromanb@pitt.edu
Committee MemberChapman, Deborah L.dlc7@pitt.edudlc7@pitt.edu
Committee MemberDavidson, Lancelad43@pitt.edulad43@pitt.edu
Committee MemberBrodsky, Jeffreyjbrodsky@pitt.edujbrodsky@pitt.edu
Date: 31 January 2012
Date Type: Publication
Defense Date: 15 November 2011
Approval Date: 31 January 2012
Submission Date: 7 December 2011
Release Date: 31 January 2012
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 147
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Shroom, Shroom2, morphology, Rho-kinase, Rock, angiogenesis, centrosome
Additional Information: This updated ETD contains the proper "Kenneth P. Dietrich School of Arts and Sciences"
Date Deposited: 31 Jan 2012 20:20
Last Modified: 16 Jul 2014 21:04
URI: http://d-scholarship.pitt.edu/id/eprint/10780

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