INTERPLAY BETWEEN POLYCYSTIN-1 AND EXTRACELLULAR MATRIX: INVESTIGATING THE REJ DOMAIN'S SIGNIFICANCE IN ADPKD PATHOGENESIS

Main Article Content

Hala Salim Sonbol, Aljazi Abdullah Alrashidi

Keywords

Polycystin-1, Receptor of the egg jelly (REJ) domain, Pull-down technique, MALDI-TOF MS, Extracellular matrix (ECM)

Abstract





Polycystin 1 (PC1) plays a crucial role in the progression of autosomal dominant polycystic kidney disease (ADPKD), a potentially life-threatening monogenic disorder marked by the gradual formation of fluid-filled cysts that compromise renal function and may lead to end-stage renal disease. Polycystin 1 is a protein of structural complexity, featuring numerous domains and engaging in diverse functions such as cellular adhesion, signal transduction, and ion channel activity. Our goal was to unravel its interactions with other proteins and its involvement in the onset of cystic diseases, ADPKD. This exploration seeks to enhance our grasp of the intricate interplay between its structure and functions, offering valuable insights into potential therapeutic targets. Our focus in this study is to study and characterize a REJ domain located at the N-terminal extracellular region of PC-1 and study its interaction with various components of the extracellular matrix. By exploring these interactions, we can better understand their potential significance in both the healthy development of the kidneys and the underlying mechanisms of ADPKD. In vitro, pull-down assays were used to assess the binding of the REJ fusion to several ECM components. The results showed that the REJ fusion protein binds to collagen VI, integrin, and fibronectin. The addition of the REJ fusion protein to HEK293 embryonic kidney epithelial cells in culture resulted in a significant reduction in the rate of cell proliferation. These findings indicated that the REJ region serves as a mediator for the interaction between polycystin-1 and the ECM and highlights the functional role of polycystin-1 in cell-matrix and cell-cell interactions.





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