The Culprit of Neuronal Degenerative Disorders: Exploring UNC79-protein Interactions and Ion Channel Mutations

In recent studies, there have been several cases globally of neuronal and behavioral defective individuals with certain phenotypic characteristics distinct from Alzheimer\u27s, autism, or other neurological disorders. The main culprit is suspected to be mutations in a protein in the brain called UNC80 that affects ion concentrations and cell signaling. The current hypothesis for the UNC80 mechanism is that it interacts with the NALCN channel and the UNC79 protein; and when defective, the complex malfunctions and lacks control over ion exchange. However, the mechanisms and how these entities work are still not fully understood. The following experiments focus on potential proteins that interact with UNC79 in particular in order to characterize the mechanisms of that one aspect of the UNC79-UNC80-NALCN complex. A yeast two-hybrid screen test and gel analysis revealed that UNC79 interacted with a number of neurological proteins, including GABARAPL1, or gamma-aminobutyric acid (GABA) A receptor-associated protein-like 1. GABARAPL1’s function increases the expression of a kappatype opioid receptor, which is linked with motor and mood control. It is suspected that GABARAPLl and UNC79 interact in a significant way to control neuronal excitability. Overall, the experiments conducted focus on characterizing potential proteins that interact with UNC79. Analyzing the sequences of known interacting protein variants gives further insight on what is going on a cellular scale, how mutations, especially those found in defective individuals, alter the UNC79-UNC80-NALCN complex, and ultimately how these changes correlate (or not) with behavioral defects