The cystic fibrosis transmembrane conductance regulator (CFTR) constitutes an ohmic chloride channel, the gating of which is dependent on cAMP-dependent phosphorylation of a regulatory (R) domain and ATP binding and hydrolysis by two nucleotide binding domains (NBDs). Previous studies have suggested that CFTR activation results from PKA phosphorylation of the R-domain, which either relieves its inhibition of the channel, or induces a positive catalytic effect of this domain on ATP dependent gating. In this study, the function of the R-domain was examined using a CFTR variant lacking the entire R-domain. These split channels assemble from separate polypeptides corresponding to the two halves of CFTR after translation of a single mRNA. Even though the back half of the split CFTR channel is expressed as a core glycosylated protein, both halves are able to fold independently and associate with one another to form a PKA-independent, constitutively active channel; however, this occurs with low efficiency. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.78387 |
| Date | January 2002 |
| Creators | Irvine, Thomas |
| Contributors | Hanrahan, John (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 Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001974777, proquestno: AAIMQ88222, Theses scanned by UMI/ProQuest. |
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