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Developing the polycystic kidney disease interactome

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thesis
posted on 27.05.2022, 22:14 authored by Mackenzie Brauer

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disease causing numerous renal cysts to form leading to adult renal failure. The PKD-causing genes, polycystic kidney disease-1 and -2 (PKD1 and PKD2), encode for proteins polycystin-1 and -2 (PC1 and PC2). These proteins form a complex through their C-termini at cilia with mutations abolishing their interaction and impairing ciliary localization. We report the first use of proximity-dependent biotinylation for identification (BioID) to  characterize the PC1 PC2 C-terminal complex binding partners in HEK 293 cells. We identify high- confidence interacting partners including an enrichment of cilia-related, transporter activity and  trafficking genes. We report interesting PC1 interactions including Biogenesis of Lysosome-Related Organelles Complex-1 (BLOC-1) subunits and BLOC-One-Related Complex (BORC) subunits. We also report endoplasmic reticulum (ER)-related proteins that likely contribute to PC2 ER localization and function. Overall, this research hopes to contribute information to how PC1 and PC2 traffic and function at cilia.


History

Language

English

Degree

Master of Science

Program

Molecular Science

Granting Institution

Ryerson University

LAC Thesis Type

Thesis

Thesis Advisor

Gagan D. Gupta