{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Gap Junctional Conductance Produced by Cx50, but not Cx46, is Regulated by the PI3K Signaling Pathway","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/76494"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Gap junction channels and cell signaling are essential components for proper organ development in multicellular organisms. The ocular lens is one such organ that has been well studied because of its large dependence on intercellular communication. The lens relies heavily on gap junction channels for intercellular communication during growth and differentiation due to the absence of a vascular system.  Gap junctions are comprised of hexameric oligomers of connexin subunits that are inserted into the plasma membrane. Genetic knockouts of lens connexins have helped to identify the function of each connexin. Cx46 knockout mice developed severe nuclear cataracts. Targeted deletion of Cx50 resulted in mild nuclear cataracts and a significant ocular growth defect not seen in the Cx46 deletion mutants. In lenses with a functional replacement of Cx50 with Cx46 knocked in to the Cx50 coding region, transparency is restored, however, the growth defect was not rescued. These results suggested that Cx46 and Cx50 lack redundancy and demonstrated the possibility that Cx50, specifically, was involved in regulation of lens growth. Previous experiments showed the MAPK signaling pathway differentially regulated Cx50 and Cx46 by altering Cx50 junctional conductance with no effect on Cx46 mediated coupling. This supports the hypothesis that Cx50, but not Cx46, is interacting with growth signaling pathways and that this signaling regulates Cx50 gap junctions specifically in a manner that modulates their activity.  This dissertation addresses the effects of PI3K signaling on gap junctional conductance produced by Cx50 and Cx46. Connexin expressing HeLa cells were incubated with inhibitors of either the PI3K catalytic subunit, p110\u00ce\u00b1, or its downstream effector, Akt. There was a three-fold decrease in Cx50-mediated gap junctional conductance when treated with either inhibitor. Gap junctional conductance of Cx46 transfected cells were unaffected by inhibitor treatment. Cx50 expressing oocytes showed increased junctional coupling when co-expressed with a constitutively active PI3K subunit and had no effect on Cx46 mediated coupling. Single channel currents of Cx50 expressing HeLa cells were measured after inhibitor treatment. Neither inhibitor had any effect on the unitary conductance. These results suggest that PI3K signaling regulates Cx50, specifically, by a mechanism other than altering its unitary conductance."},{"label":"dcterms.available","value":"2017-09-20T16:50:25Z"},{"label":"dcterms.contributor","value":"White, Thomas W"},{"label":"dcterms.creator","value":"Martinez, Jennifer Marie"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:50:25Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:50:25Z"},{"label":"dcterms.description","value":"Department of Molecular and Cellular Biology."},{"label":"dcterms.extent","value":"99 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/76494"},{"label":"dcterms.issued","value":"2015-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:50:25Z (GMT). No. of bitstreams: 1\nMartinez_grad.sunysb_0771E_12480.pdf: 2162603 bytes, checksum: fda6b6c9f9f5feac2b0e2ac4560e900b (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Akt, connexin, Cx46, Cx50, Gap junction, PI3K signaling"},{"label":"dcterms.title","value":"Gap Junctional Conductance Produced by Cx50, but not Cx46, is Regulated by the PI3K Signaling Pathway"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/41%2F65%2F11%2F41651106062952639562456765304606549800/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/41%2F65%2F11%2F41651106062952639562456765304606549800","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}