Neuronal excitability is controlled by multiple ion channels at the plasma membrane of neurons. Recently, the Na+ leak channel, NCA in C. elegans and NALCN in M. Musculus, has been identified as the molecular entity responsible for the background Na+ leak at rest in neurons. In this thesis, I show that NLF-1 (NCA Localization Factor) and mouse NLF-1, a group of newly defined, uncharacterized proteins, are endoplasmic reticular proteins required for the trafficking of NCA-1 and NCA-2 to their target axonal membrane. In primary mouse cortical neurons, knockdown of mNLF-1 partially abolishes the background Na+ leak current. Furthermore, NLF-1 and mNLF-1 directly interact with domain II S5/P-loop/S6 of NALCN through a membrane yeast-two-hybrid assay. In C. elegans, this region is required in vivo in NCA-1 for it’s trafficking. Finally, I identify novel NLF-1 interacting partners through a MYTH assay.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/42662 |
| Date | 20 November 2013 |
| Creators | Alcaire, Salvador |
| Contributors | Zhen, Mei |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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