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<https://discovery.ucl.ac.uk/id/eprint/1306879> <http://purl.org/dc/terms/title> "Identification of regulators and effectors of RhoGTPase signalling in corneal epithelial cells"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/1306879> <http://purl.org/ontology/bibo/abstract> "Epithelial cells adhere to each other and are connected via a series of junctions.\r\nTight junctions (TJs) are a specific type of junction consisting of heteromeric\r\nprotein complexes that are linked to the actin cytoskeleton and are important in\r\nregulating paracellular permeability and cell polarity. RhoGTPases are small\r\nmolecular switch proteins that are important regulators of the cytoskeleton and\r\nmodulators of gene expression. RhoGTPases have thus been identified as\r\nbeing major signalling components associated with TJs. However little is known\r\nabout how RhoGTPases are regulated to control junction formation and gene\r\nexpression in corneal epithelial cells. I used a siRNA screening approach\r\ncombined with functional assays to identify components of RhoGTPase\r\nsignalling that affect the assembly of junctions and gene expression in Human\r\ncorneal epithelial cells (HCE). I identified and validated several candidates that\r\nregulate junction assembly. One of these candidates was p114RhoGEF, a\r\nnovel TJ localised guanine nucleotide exchange factor (GEF) important for the\r\nassembly of functional TJs. p114RhoGEF is a widely expressed and I\r\ndiscovered its depletion effects junction formation and morphogenesis in three\r\ndimensional culture systems in different epithelial cell types. p114RhoGEF is\r\nrequired for activation of RhoA at cell-cell junctions and junctional actinomyosin\r\nactivity, p114RhoGEF is present in a complex containing Myosin II-A, the RhoA\r\neffector Rock II and the junctional adaptor protein Cingulin; indicating\r\np114RhoGEF is a component of a junction associated RhoA-signalling module.\r\np114RhoGEF, thus regulates spatial activation of RhoA at cell-cell junctions\r\nand organisation of the junctional cytoskeleton. p114RhoGEF may also have a\r\nrole in cell migration, as depletion in HCE cells, caused cells to migrate at a slower rate during wound healing assays. I have also started to explore the\r\nfunction of a putative p114RhoGEF ortholog, cg10188 in Drosophila\r\nmelanogaster. Preliminary experiments have identified cg10188 to be important\r\nin larval development."^^<http://www.w3.org/2001/XMLSchema#string> .
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