A Conserved Family of ER Proteins NLF Regulate the Na+ Leak Channel NCA/NALCN in Caenorhabditis elegans and Mus musculus

• Main Author: Alcaire, Salvador
• Other Authors: Zhen, Mei
• Language: en_ca
• Published: 2013
• Subjects: ER protein; trafficking; leak channel; 0317; 0307
• Online Access: http://hdl.handle.net/1807/42662

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.