Gap junctions are membrane channels between closely apposed cells that allow for intercellular exchange of small molecules. These channels are formed from a family homologous proteins known as connexins (Cx). In the present study we studied connexin trafficking within the cell with particular emphasis on 1/ the mechanisms of gap junction formation and removal and on 2/ the early events associated with connexin biosynthesis. The mechanisms of gap junction formation and removal were studied by treating Normal Rat Kidney and BICR-MlR$ sb{ rm k}$ rat mammary tumour cells with ilimaquinone (IQ), a novel and reversible inhibitor of protein secretion. The effects of IQ treatment on Cx43 maturation and gap junction assembly were then examined. The events associated with biosynthesis were examined through localization of Cx32 messenger RNA to either free or membrane-bound polyribosomes in rat liver hepatocytes through Northern blot analysis. In these studies we observed that IQ inhibited gap junction formation without inhibiting trafficking of Cx43 to the cell surface. Upon removal of the drug, gap junction plaques reformed. We concluded that additional factors other than phosphorylation are necessary for Cx43 assembly into gap junctions and this process is independent of microtubules. Preliminary studies revealed Cx32 mRNA in populations of free and membrane-bound polyribosomes suggesting that Cx32 is inserted into the endoplasmic reticulum membrane both post- and co-translationally.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.23886 |
| Date | January 1995 |
| Creators | Feldman, Paul Andrew |
| Contributors | Laird, Dale (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Anatomy and Cell Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001481300, proquestno: MM12192, Theses scanned by UMI/ProQuest. |
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