Decoding Polycystin-1's G-Proteolytic Site: Implications for Cell Interactions and Autosomal Dominent Polycystic Kidney Disease Pathogenesis

Hala Salim Sonbol; Alaa Muqbil Al-sirhani

doi:10.61091/jpms202413417

Author(s)

Hala Salim Sonbol Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 80200, Saudi Arabia.

Alaa Muqbil Al-sirhani Chemistry Department, Faculty of Sience, Jouf University, Sakaka, 2014 Saudi Arabia.

Abstract

Renal cysts are the outcome of ADPKD, which is characterised by abnormal cell proliferation, altered cellular polarity, and disordered extracellular matrix dynamics. Of ADPKD instances, the PKD1 gene mutation is responsible for about 85% of cases. The goal of this study is to better understand the function of polycystin-1, a membrane protein with unique peptide domains involved in interactions between cells and matrices, and the G-proteolytic site domain (GPS). Their importance in normal kidney development and the underlying mechanisms of ADPKD pathophysiology may be revealed by this interaction. In order to characterize MBP-GPS's function, its effect on the growth of human embryonic kidney epithelial cells (HEK-293) was investigated. The results showed that when the fusion protein was exposed to cells, the rates of cell proliferation significantly decreased in a dose-dependent manner. In addition, pull-down studies using MBP-GPS were carried out on HEK-293 cells in order to find potential interaction proteins connected to the GPS domain. Matrix-assisted laser desorption/ionization timeof-flight (MALDI-TOF) mass spectrometry was utilised to identify the peptides that emerged from tryptic digestion after the cell lysate underwent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Among the candidate proteins identified, laminin emerged as a potential interacting partner with the GPS domain. This research represents a significant step towards unraveling the nature of the putative interactions between the extracellular domains of ECM and the polycystin-1, shedding light on their potential roles in ADPKD development.

Publication Details

Page(s) 112-120

DOI 10.61091/jpms202413417

Published Journal: Journal of Pioneering Medical Sciences, Volume: 13, Issue: 4, Year: 2024

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Keywords

polycystin-1, ADPKD, G-proteolytic site (GPS) domain

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