Nitti, Maria (2013) Interfering with Rac1 activity in FRT thyroid epithelial cells impairs the expression of the polarized phenotype and of the E-cadherin function. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: Interfering with Rac1 activity in FRT thyroid epithelial cells impairs the expression of the polarized phenotype and of the E-cadherin function
Date: 2 April 2013
Number of Pages: 113
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
Avvedimento, Vittorio
Date: 2 April 2013
Number of Pages: 113
Keywords: Cell polarity
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/13 - Biologia applicata
Date Deposited: 10 Apr 2013 13:48
Last Modified: 17 Jun 2014 06:05

Collection description

The acquisition of cell polarity, which includes the establishment of the tight junction barrier, polarized assembly of the cytoskeleton and appropriate organization of membrane traffic, requires external cues, that in epithelial cells are represented by the interaction of cells with their neighbors and with the extracellular matrix. The Rho family of small GTPases, regulate many biological processes including cell cycle progression, apoptosis, migration and intercellular adhesion. We focused on the analysis of the role of Rac1 protein in the acquisition and maintenance of the polarized phenotype in the FRT rat thyroid epithelial cell line. In this work a novel experimental approach, i.e. the use of an inducible dominant-negative form of the Rac1 protein, ER-Rac1N17, was used to demonstrate the involvement of this small GTPase in the epithelial polarization process and to unravel its mechanism of action. Oriented cell migration, transepithelial resistance acquisition, and formation of polarized cysts in suspension cultures were investigated. All these parameters are related to the polarized phenotype and were found to be affected after inhibition of Rac1 activity. To unravel the molecular mechanism by which Rac1 affected cell polarity, we investigated the establishment of E-cadherin-dependent cell-cell contacts, which is another key event in the process of epithelial polarization, by calcium switch assays. We determined the dynamics of subcellular localization of Rac1 and of E-cadherin molecules to understand if, and how, the two proteins were intimately related functionally. We conclude that Rac1 inhibition affects cell polarity by impairing E-cadherin recycling to the plasma membrane.


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