Analyzing the Role of a Novel Transmembrane Protein in Rhodopsin-Deficient Drosophila Photoreceptors
Author ORCID Identifier
0000-0002-3742-9746
Date of Award
Summer 8-31-2025
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
Kellee R. Siegfried-Harris, Manickam Sugumaran, Johannes von Lintig
Abstract
Vitamin A (vitA) is an essential nutrient and a precursor of the retinal chromophore, which is necessary for photoreceptor development and function. Chronic vitA deficiency causes photoreceptor death and is the leading cause of preventable childhood blindness. Like humans, Drosophila melanogaster requires vitA for Rhodopsin synthesis and vision but not for essential developmental processes or survival. Since chronic vitA deprivation in Drosophila does not lead to photoreceptor death, I hypothesized that an unknown molecular mechanism preserves photoreceptor structure and visual function.
In collaboration with the Shevchenko lab (MPI Dresden, Germany), I identified the novel transmembrane protein Mps, which responds to vitA deficiency and preserves the structure of Rhodopsin-deficient photoreceptor neurons. First, to understand how Mps is regulated, I analyzed Drosophila mutants with defective Rhodopsin 1 (Rh1) synthesis, ER stress, and malformed light-sensing compartments (rhabdomeres). While it has been challenging to identify a single causative factor, Mps expression strongly correlates with Rh1 processing defects and degradation. Second, I analyzed the function of a potential interactor of Mps, the scaffolding protein InaD. My data suggest that Mps anchors InaD to the rhabdomere membrane before the onset of Rh1 expression and that this Mps-InaD interaction is maintained in Rh1-deficient membranes to stabilize the rhabdomeres.
Taken together, these insights reveal how the interaction of a transmembrane protein and a scaffolding protein promote the survival of damaged photoreceptor neurons and could inspire novel therapeutic approaches to treat eye diseases.
Recommended Citation
Lam-Kamath, Khanh B., "Analyzing the Role of a Novel Transmembrane Protein in Rhodopsin-Deficient Drosophila Photoreceptors" (2025). Graduate Doctoral Dissertations. 1090.
https://scholarworks.umb.edu/doctoral_dissertations/1090
Comments
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