Minnet Zerisenai
Pronouns: She/Her/Hers
Research Mentor(s): Brett McCray
Research Mentor School/College/Department: Neurology / Medicine
Program:
Authors: Minnet Zerisenai, Linh Vo, Gage Kosmanopoulos, Brett McCray
Session: Session 2: 10:00 am – 10:50 am
Poster: 3
Abstract
Channelopathies that occur due to mutations in the TRPV4 calcium permeable ion channel lead to several diseases including neuropathy, skeletal dysplasia, and arthropathy. These mutations have been shown to result in gain-of-function effects on the TRPV4 ion channel function, allowing for an influx of calcium into cells and downstream cellular toxicity. However, it is unknown how the differences between the mutations affect basic channel function in TRPV4, and whether they have different effects on the amount of calcium within the cells. In this project, plasmids encoded with GFP-tagged TRPV4 (WT and mutant) were utilized to transfect the mutated TRPV4 into motor neuron-like cells to examine their behavior when stimulated. TRPV4 was then stimulated using a hypotonic solution and calcium imaging was utilized to determine baseline and stimulated channel activity. The ion channel activity of neuropathy and skeletal dysplasia causing TRPV4 mutants was compared to determine if there are functional properties that may account for the different types of diseases. The baseline and stimulated calcium results of the WT TRPV4 were analyzed and compared to the calcium results of the skeletal dysplasia and neuropathy mutants. We found that both the neuropathy and skeletal dysplasia mutant TRPV4 showed augmented responses to stimulation compared to WT TRPV4. After conducting this experiment, we discovered that the amount of calcium varied between mutations, indicating that they have contrasting effects on the amount of calcium released. In our next steps, we will compare the functional properties of the mutants in other cell types and obtain an understanding of how the neuropathy and skeletal dysplasia mutants differ in their gain-of-function effect on TRPV4. These experiments will inform therapeutic strategies to target TRPV4 in various disease states among patients.
