Date of Award

8-2024

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology/Molecular, Cellular, and Organismal Biology

First Advisor

Jens Rister

Second Advisor

Alexey Veraksa

Third Advisor

Linda Huang, Catherine McCusker, Johannes von Lintig

Abstract

Vitamin A is essential for vision and must be obtained through our diet. Vitamin A deprivation (VAD) severely disrupts the morphology of photoreceptors, causes a loss of light-sensing pigments, and is the leading cause of preventable childhood blindness. However, even chronic VAD in Drosophila melanogaster does not lead to photoreceptor death, which led us to hypothesize that an unknown mechanism stabilizes damaged photoreceptors to preserve visual function. To understand this stabilizing mechanism and identify its components, we employed transcriptomics and proteomics to investigate the molecular consequences of VAD in Drosophila. Through these studies, we discovered a set of factors exhibiting differential expression levels in response to VAD. These factors are involved in various cellular processes, including phototransduction, Rhodopsin processing, translation, and the TCA cycle. Among these factors, we identified a novel transmembrane protein, which we named Mps (My Precious Stabilizer). Mps is highly upregulated in vitamin A-deficient Drosophila photoreceptors and stabilizes their light-sensing compartments by interacting with the photoreceptor-specific scaffolding protein InaD. Furthermore, Mps is normally required during development and genetically interacts with InaD. These findings deepen our understanding of how the eye responds to environmental stresses and could inspire novel therapeutic approaches for treating human eye diseases.

Comments

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