Department or Program

Neuroscience

Abstract

Intracellular signaling depends on the precise regulation of calcium and phosphoinositide lipids. The IP3R-binding protein IRBIT, first described as an inhibitor of IP3-mediated calcium release, has recently been shown to interact with PIPKs. This suggests a direct role of IRBIT in phosphoinositide metabolism. This research adds to the larger hypothesis that IRBIT coordinates Ca2+ release and phosphoinositide turnover, creating a feedback loop critical for neuronal signaling. The aim of this study is to determine the phosphoinositide levels and the kinetics of phosphoinositide metabolism in wild-type and IRBIT-/- HEK293 cells. I hypothesize that I will find altered basal phosphoinositide levels and/or altered kinetics of phosphoinositide synthesis in IRBIT-/- HEK293 cells. Lipid mass spectrometry provides high-sensitivity detection of individual phosphoinositides, while live-cell confocal imaging with fluorescent lipid-binding probes tracks dynamic PI(4,5)P2 recovery. Preliminary data reveal altered PIP2 species and PI:PIP2 ratios in IRBIT-deficient cells, supporting a regulatory role for IRBIT, while a quantitative analysis of total phosphoinositide levels in this study did not reveal significantly different amounts between wild-type and IRBIT-/- cells under the conditions tested. Because disruptions in phosphoinositide signaling underlie prevalent disorders such as epilepsy, Alzheimer’s disease, and Parkinson’s disease, defining IRBIT’s contribution could bring light to new therapeutic targets for these widespread neurological conditions.

Level of Access

Restricted: Campus/Bates Community Only Access

First Advisor

Kruse, Martin

Date of Graduation

5-2026

Degree Name

Bachelor of Science

Number of Pages

69

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